Molecules

8 pages, 1326 KiB

Open AccessArticle

Synthesis and Anticancer Cytotoxicity of Azaaurones Overcoming Multidrug Resistance

by Szilárd Tóth, Áron Szepesi, Viet-Khoa Tran-Nguyen, Balázs Sarkadi, Katalin Német, Pierre Falson, Attilio Di Pietro, Gergely Szakács and Ahcène Boumendjel

Molecules 2020, 25(3), 764; https://doi.org/10.3390/molecules25030764 - 10 Feb 2020

Cited by 18 | Viewed by 4100

Abstract

The resistance of tumors against anticancer drugs is a major impediment for chemotherapy. Tumors often develop multidrug resistance as a result of the cellular efflux of chemotherapeutic agents by ABC transporters such as P-glycoprotein (ABCB1/P-gp), Multidrug Resistance Protein 1 (ABCC1/MRP1), or Breast Cancer [...] Read more.

The resistance of tumors against anticancer drugs is a major impediment for chemotherapy. Tumors often develop multidrug resistance as a result of the cellular efflux of chemotherapeutic agents by ABC transporters such as P-glycoprotein (ABCB1/P-gp), Multidrug Resistance Protein 1 (ABCC1/MRP1), or Breast Cancer Resistance Protein (ABCG2/BCRP). By screening a chemolibrary comprising 140 compounds, we identified a set of naturally occurring aurones inducing higher cytotoxicity against P-gp-overexpressing multidrug-resistant (MDR) cells versus sensitive (parental, non-P-gp-overexpressing) cells. Follow-up studies conducted with the P-gp inhibitor tariquidar indicated that the MDR-selective toxicity of azaaurones is not mediated by P-gp. Azaaurone analogs possessing pronounced effects were then designed and synthesized. The knowledge gained from structure–activity relationships will pave the way for the design of a new class of anticancer drugs selectively targeting multidrug-resistant cancer cells. Full article

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16 pages, 3030 KiB

Open AccessArticle

Discrimination of Cultivated Regions of Soybeans (Glycine max) Based on Multivariate Data Analysis of Volatile Metabolite Profiles

by So-Yeon Kim, So Young Kim, Sang Mi Lee, Do Yup Lee, Byeung Kon Shin, Dong Jin Kang, Hyung-Kyoon Choi and Young-Suk Kim

Molecules 2020, 25(3), 763; https://doi.org/10.3390/molecules25030763 - 10 Feb 2020

Cited by 11 | Viewed by 4315

Abstract

Soybean (Glycine max) is a major crop cultivated in various regions and consumed globally. The formation of volatile compounds in soybeans is influenced by the cultivar as well as environmental factors, such as the climate and soil in the cultivation areas. [...] Read more.

Soybean (Glycine max) is a major crop cultivated in various regions and consumed globally. The formation of volatile compounds in soybeans is influenced by the cultivar as well as environmental factors, such as the climate and soil in the cultivation areas. This study used gas chromatography-mass spectrometry (GC-MS) combined by headspace solid-phase microextraction (HS-SPME) to analyze the volatile compounds of soybeans cultivated in Korea, China, and North America. The multivariate data analysis of partial least square-discriminant analysis (PLS-DA), and hierarchical clustering analysis (HCA) were then applied to GC-MS data sets. The soybeans could be clearly discriminated according to their geographical origins on the PLS-DA score plot. In particular, 25 volatile compounds, including terpenes (limonene, myrcene), esters (ethyl hexanoate, butyl butanoate, butyl prop-2-enoate, butyl acetate, butyl propanoate), aldehydes (nonanal, heptanal, (E)-hex-2-enal, (E)-hept-2-enal, acetaldehyde) were main contributors to the discrimination of soybeans cultivated in China from those cultivated in other regions in the PLS-DA score plot. On the other hand, 15 volatile compounds, such as 2-ethylhexan-1-ol, 2,5-dimethylhexan-2-ol, octanal, and heptanal, were related to Korean soybeans located on the negative PLS 2 axis, whereas 12 volatile compounds, such as oct-1-en-3-ol, heptan-4-ol, butyl butanoate, and butyl acetate, were responsible for North American soybeans. However, the multivariate statistical analysis (PLS-DA) was not able to clearly distinguish soybeans cultivated in Korea, except for those from the Gyeonggi and Kyeongsangbuk provinces. Full article

(This article belongs to the Special Issue Progress in Volatile Organic Compounds Research)

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Graphical abstract

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Full article ">Figure 1
Partial least square-discriminant analysis (PLS-DA) score plot of soybean samples from different cultivation areas; (a) 3D score plot; (b) score plot PLS[<a href="#B1-molecules-25-00763" class="html-bibr">1</a>]-PLS[<a href="#B2-molecules-25-00763" class="html-bibr">2</a>], indicating the separation between different cultivation areas. Full article ">Figure 1 Cont.
Partial least square-discriminant analysis (PLS-DA) score plot of soybean samples from different cultivation areas; (a) 3D score plot; (b) score plot PLS[<a href="#B1-molecules-25-00763" class="html-bibr">1</a>]-PLS[<a href="#B2-molecules-25-00763" class="html-bibr">2</a>], indicating the separation between different cultivation areas. Full article ">Figure 2
Heatmap generated by a hierarchical clustering analysis of 146 metabolites. Full article ">Figure 3
PLS-DA score plot of soybeans from Korea on the basis of volatile metabolites: (a) 3D score plot; (b) score plot PLS[<a href="#B1-molecules-25-00763" class="html-bibr">1</a>]-PLS[<a href="#B2-molecules-25-00763" class="html-bibr">2</a>]. GGIC—Gyeonggi province Anseong, GGAS—Gyeonggi province Icheon, GWCC—Gangwon province Chuncheon, GWYW—Gangwon province Yeongwol, CBES—Chungcheongbuk province Eumseong, CNCA— Chungcheongnam province Cheonan, CNGJ—Chungcheongnam province Gongju, JBGJ—Jeollabuk province Gimje, JBIS—Jeollabuk province Imsil, JNNJ—Jeollanam province Naju, JNYG—Jeollanam province Yeonggwang, KBCD—Kyeongsangbuk province Cheongdo, KBES—Kyeongsangbuk province Uiseong, KBYC—Kyeongsangbuk province Yeongcheon, KNCN—Kyeongsangnam province Changnyeong, KNMY—Kyeongsangnam province Miryang, KNGC—Kyeongsangnam province Geochang. Full article ">

35 pages, 1953 KiB

Open AccessReview

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

by Camila R. Ferraz, Thacyana T. Carvalho, Marília F. Manchope, Nayara A. Artero, Fernanda S. Rasquel-Oliveira, Victor Fattori, Rubia Casagrande and Waldiceu A. Verri, Jr.

Molecules 2020, 25(3), 762; https://doi.org/10.3390/molecules25030762 - 10 Feb 2020

Cited by 176 | Viewed by 17127

Abstract

Pathological pain can be initiated after inflammation and/or peripheral nerve injury. It is a consequence of the pathological functioning of the nervous system rather than only a symptom. In fact, pain is a significant social, health, and economic burden worldwide. Flavonoids are plant [...] Read more.

Pathological pain can be initiated after inflammation and/or peripheral nerve injury. It is a consequence of the pathological functioning of the nervous system rather than only a symptom. In fact, pain is a significant social, health, and economic burden worldwide. Flavonoids are plant derivative compounds easily found in several fruits and vegetables and consumed in the daily food intake. Flavonoids vary in terms of classes, and while structurally unique, they share a basic structure formed by three rings, known as the flavan nucleus. Structural differences can be found in the pattern of substitution in one of these rings. The hydroxyl group (–OH) position in one of the rings determines the mechanisms of action of the flavonoids and reveals a complex multifunctional activity. Flavonoids have been widely used for their antioxidant, analgesic, and anti-inflammatory effects along with safe preclinical and clinical profiles. In this review, we discuss the preclinical and clinical evidence on the analgesic and anti-inflammatory proprieties of flavonoids. We also focus on how the development of formulations containing flavonoids, along with the understanding of their structure-activity relationship, can be harnessed to identify novel flavonoid-based therapies to treat pathological pain and inflammation. Full article

(This article belongs to the Special Issue Flavonoids and Their Disease Prevention and Treatment Potential)

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12 pages, 3002 KiB

Open AccessArticle

Direct Recovery of the Rare Earth Elements Using a Silk Displaying a Metal-Recognizing Peptide

by Nobuhiro Ishida, Takaaki Hatanaka, Yoichi Hosokawa, Katsura Kojima, Tetsuya Iizuka, Hidetoshi Teramoto, Hideki Sezutsu and Tsunenori Kameda

Molecules 2020, 25(3), 761; https://doi.org/10.3390/molecules25030761 - 10 Feb 2020

Cited by 3 | Viewed by 4016

Abstract

Rare earth elements (RE) are indispensable metallic resources in the production of advanced materials; hence, a cost- and energy-effective recovery process is required to meet the rapidly increasing RE demand. Here, we propose an artificial RE recovery approach that uses a functional silk [...] Read more.

Rare earth elements (RE) are indispensable metallic resources in the production of advanced materials; hence, a cost- and energy-effective recovery process is required to meet the rapidly increasing RE demand. Here, we propose an artificial RE recovery approach that uses a functional silk displaying a RE-recognizing peptide. Using the piggyBac system, we constructed a transgenic silkworm in which one or two copies of the gene coding for the RE-recognizing peptide (Lamp1) was fused with that of the fibroin L (FibL) protein. The purified FibL-Lamp1 fusion protein from the transgenic silkworm was able to recognize dysprosium (Dy³⁺), a RE, under physiological conditions. This method can also be used with silk from which sericin has been removed. Furthermore, the Dy-recovery ability of this silk was significantly improved by crushing the silk. Our simple approach is expected to facilitate the direct recovery of RE from an actual mixed solution of metal ions, such as seawater and industrial wastewater, under mild conditions without additional energy input. Full article

(This article belongs to the Special Issue Silk Fibroin Materials)

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Breeding of the transgenic silkworm. (a) Construction of the expression vector. Each plasmid contains expression units for selection marker gene (DsRed2) and cDNA of fibroin L-chain (FibL cDNA) between the piggyBac inverted terminal repeat (ITR). Three gene fragments containing Lamp1 or His Tag were inserted into the 3’ ends of FibL cDNA using restriction site of BamH I and Hind III. 3xP3 pro., 3xP3 promoter; SV40 polyA, polyA signal of SV40; FibLpro., promoter of fibroin L-chain; and FibL 3’ UTR, 3’ untranslated region of fibroin L-chain. (b) SDS-PAGE analysis of purified FibL-Lamp1-His protein from Ex1 strain and the control strain. (c) Western blotting analysis using Lamp1, and His-tag antibody. Each arrow indicates the expected molecular weight of the target protein. Lane 1, FibL sample before purification; Lane 2, flow-through of FibL column; Lane 3, purified FibL; Lane 4, buffer; Lane 5, FibL-Lamp1 sample before purification; Lane 6, flow-through of FibL-Lamp1 column; and Lane 7, purified FibL-Lamp1. Full article ">Figure 2
Dy3+ recognition with purified FibL-Lamp1-His protein. (a) Optical image of precipitation induced with protein adding. (b) SEM image of precipitation. Scale bar, 100 µm. (c) EDX spectrum. The red frame area in the SEM image of (b) was analyzed. Each arrow indicates the spectrum of Dy. (d) Elemental mapping of SEM image (Dy, dysprosium; N, nitrogen; and S, sulfur). Scale bar, 100 µm. Full article ">Figure 3
La3+ and Lu3+ recognition with the purified FibL-Lamp1-His protein. (a–c) Reaction with La3+, and (d–f) reaction with Lu3+. (a–d) Optical image of precipitation induced by the purified FibL-Lamp1-His protein. (b–e) SEM image (left) and elemental mapping image (right) of precipitation. Scale bars, 100 µm. (c–f) EDX spectrum. The red frame area in the SEM image was analyzed. Each arrow indicates the spectrum of La or Lu. Full article ">Figure 4
The recovery efficiency of Dy3+ with the purified protein. The supernatant solution after reaction (mentioned in <a href="#molecules-25-00761-f002" class="html-fig">Figure 2</a>a) was collected, and the Dy3+ concentration in the solution was determined. Average and standard deviations from three independent experiments were represented. Full article ">Figure 5
RE recovery process with silk powder: (a) Schematic diagram of the process for RE-recovery, and optical image of the prepared silk and (b) SEM image of roughly crushed silk. Full article ">Figure 6
Dy3+ recognition with silk powder: (a) SEM (left) and elemental mapping (right) images of silk powder after Dy3+ absorption reaction. The yellow signal indicates a Dy. Scale bar, 80 µm, (b) EDX spectrum, each arrow indicates the Dy signal and (c) the recovery efficiency of Dy3+ of silk with harvested silk from Ex2-2. Averages and standard deviations for three independent experiments were represented. Full article ">Figure 7
Reusability of silk powder for Dy3+ recovery. (a) The relative degree to the initial Dy3+ recovery efficiency is shown. Averages and standard deviations for three independent experiments were represented. (b) SEM-EDX analysis, the captured Dy (yellow signal) was eluted with acetic buffer (50 mM) at pH 4.0, and the silk powder was recycled. Scale bars: 100 µm. Full article ">

19 pages, 5817 KiB

Open AccessArticle

Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-β-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p

by Camila Hernandes, Lucyene Miguita, Romario Oliveira de Sales, Elisangela de Paula Silva, Pedro Omori Ribeiro de Mendonça, Bruna Lorencini da Silva, Maria de Fatima Guarizo Klingbeil, Monica Beatriz Mathor, Erika Bevilaqua Rangel, Luciana Cavalheiro Marti, Juliana da Silva Coppede, Fabio Daumas Nunes, Ana Maria Soares Pereira and Patricia Severino

Molecules 2020, 25(3), 760; https://doi.org/10.3390/molecules25030760 - 10 Feb 2020

Cited by 17 | Viewed by 4107

Abstract

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and [...] Read more.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-β-hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-β-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications. Full article

(This article belongs to the Special Issue Natural Bioactive Molecules and Toxins from Marine and Terrestrial Origin)

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UPLC-MS chromatograms of maytenin (A-a), 22-β-hydroxymaytenin (B-b) and of dichloromethane roots extract from M. ilicifolia cultivated in vitro (C). Full article ">Figure 2
Cell viability results from MTT assay after incubation with maytenin or 22-β-hydroxymaytenin. (A) IC50 following 24 h incubation with maytenin or 22-β-hydroxymaytenin for each cell type; (B) Viability of SCC9 cell line following incubation for 6, 24, 48 or 72 h with maytenin or 22-β-hydroxymaytenin with IC50 value; (C) Viability of SCC25 cell line following incubation for 6, 24, 48 or 72 h with maytenin or 22-β-hydroxymaytenin with IC50 value; (D) Viability of FaDu cell line following incubation for 6, 24, 48 or 72 h with maytenin or 22-β-hydroxymaytenin with IC50 value. * p < 0.05, ** p < 0.01, *** p < 0.001 (one-way ANOVA). Full article ">Figure 3
Size and cell viability in maytenin and 22-β-hydroxymaytenin treated spheroids. (A) Spheroids were treated for 48 h with the corresponding IC50 obtained in 2D cell culture. No size reduction was detectable using a light microscope for any of the treatments. n = 4. (B) Cell viability in the outer layers of the spheroids following treatment with the IC50 obtained in 2D cell culture and with 10× the IC50 obtained in 2D cell culture. n = 4. Live cells fluoresce green, and dead cells fluoresce red. A clear effect on cell viability was observed at the outer cell layer when 10× the IC50 was used for every treatment. Full article ">Figure 4
Anti-proliferative effects of maytenin, 22-β-hydroxymaytenin and cisplatin measured by EdU incorporation into DNA. Column graphs (A,C,E,G) show the percentage of cells staining for EdU (red) compared to Hoechst 33,342 (blue) stained nuclei (± SD). There were two replicates in each experiment and all cells were counted for each treatment. Images (B,D,F,H) were taken on a fluorescence microscope (magnification ×20) and depict EdU incorporation (red) and Hoechst 33,342 nuclei staining. EdU incorporation occurs during DNA synthesis, EdU positive cells indicate DNA replication and consequent cell cycle progression. * p < 0.01. ** p < 0.05. Full article ">Figure 5
Effect of triterpenes on oxidative stress in SCC cell lines. (A) SCC9, Detroit and FaDu cell lines treated with cisplatin. ROS induction following cisplatin treatment is well established and these results were used as positive controls. The oxidative stress increases in tumor cells, compared with control when treated with maytenin or 22-β-hydroxymaytenin in SCC9 (B), FaDu (C) and Detroit (D). Total ROS after treatment with the IC50 value for 18 h was assessed by fluorescent probe detection using confocal microscopy. n = 2. Full article ">Figure 6
Apoptotic cell death measured by Annexin V and 7-ADD assay and caspase 3/7 activation. Keratinocytes and FaDu cell line were treated with 22-β-hydroxymaytenin, maytenin, or cisplatin and the effect on cell death induction was evaluated by flow cytometry using Annexin-V and 7-AAD staining. Keratinocytes: (A) Early apoptosis, (B) late apoptosis, (C) total cell death and (D) individual flow cytometry plots for each treatment. FaDu cell line: (E) Early apoptosis, (F) late apoptosis, (G) total cell death and (H) individual flow cytometry plots of each treatment. (I) caspase-3/7 activation in FaDu cell line following treatment by 22-β-hydroxymaytenin, maytenin, or cisplatin. Full article ">Figure 7
(A) Comparison of IC50 of maytenin for SCC9ZS GREEN and SCC9ZS GREEN LN-1. Maytenin showed similar effect in cell viability for SCC9ZS GREEN and SCC9ZS GREEN LN-1 cell lines. (B) Non-invasive in vivo imaging of mice harboring a human tumor xenograph prior and following treatment with maytenin and cisplatin: SCID mice were injected with SCC9ZS GREEN or SCC9ZS GREEN LN-1 cells and, 15 days later, mice with similar tumor burden determined by IVIS fluorescence imaging were assigned to each treatment group: control (PBS), maytenin (2 mg/Kg, i.p. Monday-Wednesday-Friday), or cisplatin (5 mg/Kg, i.p. once a week). b, c, d, f, g, h: representative IVIS images of mice from each experimental group at each stage the correspondent treatment: at 15 days following injection of cancer derived cells at the tongue mice had not received any treatment yet, at days 21 and 29, the respective treatment schemes were being applied. The graphical representation of the fluorescence in specific regions of interest in mice is indicated by a multi-color distribution: the high intensity of fluorescence appears as yellow color and low intensity of fluorescence as red. (C) Body weight of mice during the treatment cycle. There was no significant difference in body weight when maytenin and cisplatin were considered, but mice harbouring tumours derived from SCC9ZS GREEN LN-1 cells lost weight due to tumour burden. (D) Photomicrograph of mouse kidney tissues with H&E staining: For untreated mice (A1, detailed in A2 and A3) and maytenin treated mice following injection of SCC9ZS GREEN LN-1 cells at tongue (B1, detailed in B2 and B3) the cross section of kidney shows proximal tubules (PT) exhibiting brush border and distal tubules (DT) with normal morphology, the renal cortex exhibits normal glomerular (G) and tubular morphology structures. In cisplatin treated mice (C1, detailed in C2 and C3), renal cortex features suggest acute tubular necrosis as shown by patchy or diffuse denudation of the renal cells with loss of brush border (arrows), flattening of the renal tubular cells due to tubular dilation (arrowheads), pyknotic nucleus (red arrow) and loss of tubular architecture. Images illustrate the biological effects in tissue samples collected 29 days after the injection of SCC9ZS GREEN LN-1 cells. Scale bars represent 20 µm. Full article ">

18 pages, 6292 KiB

Open AccessArticle

Stabilizing the Oil-in-Water Emulsions Using the Mixtures of Dendrobium Officinale Polysaccharides and Gum Arabic or Propylene Glycol Alginate

by Bo Wang, Haiyan Tian and Dong Xiang

Molecules 2020, 25(3), 759; https://doi.org/10.3390/molecules25030759 - 10 Feb 2020

Cited by 33 | Viewed by 6784

Abstract

Coconut oil-in-water emulsions were prepared using three polysaccharides: Dendrobium officinale polysaccharide (DOP), propylene glycol alginate (PGA), gum arabic (GA) and their polysaccharide complexes as emulsifiers. The effects of the ratio of the compounded polysaccharides on their apparent viscosity and interfacial activity were explored [...] Read more.

Coconut oil-in-water emulsions were prepared using three polysaccharides: Dendrobium officinale polysaccharide (DOP), propylene glycol alginate (PGA), gum arabic (GA) and their polysaccharide complexes as emulsifiers. The effects of the ratio of the compounded polysaccharides on their apparent viscosity and interfacial activity were explored in this study. The average particle size, zeta potential, microstructure, rheological properties, and physical stability of the emulsions prepared with different compound-polysaccharides were studied. The results showed that mainly DOP contributed to the apparent viscosity of the compound-polysaccharide, while the interfacial activity and zeta potential were mainly influenced by PGA or GA. Emulsions prepared with compound-polysaccharides exhibited smaller average particle sizes, and microscopic observations showed smaller droplets and less droplet aggregation. In addition, the stability analysis of emulsions by a dispersion analyzer LUMiSizer showed that the emulsion prepared by compounding polysaccharides had better physical stability. Finally, all of the above experimental results showed that the emulsions prepared by PGA:DOP = 2:8 (total concentration = 1.5 wt%) and 2.0% GA + 1.5% DOP were the most stable. Full article

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10 pages, 2605 KiB

Open AccessReview

Bone Mineral Affinity of Polyphosphodiesters

by Yasuhiko Iwasaki

Molecules 2020, 25(3), 758; https://doi.org/10.3390/molecules25030758 - 10 Feb 2020

Cited by 16 | Viewed by 4033

Abstract

Biomimetic molecular design is a promising approach for generating functional biomaterials such as cell membrane mimetic blood-compatible surfaces, mussel-inspired bioadhesives, and calcium phosphate cements for bone regeneration. Polyphosphoesters (PPEs) are candidate biomimetic polymer biomaterials that are of interest due to their biocompatibility, biodegradability, [...] Read more.

Biomimetic molecular design is a promising approach for generating functional biomaterials such as cell membrane mimetic blood-compatible surfaces, mussel-inspired bioadhesives, and calcium phosphate cements for bone regeneration. Polyphosphoesters (PPEs) are candidate biomimetic polymer biomaterials that are of interest due to their biocompatibility, biodegradability, and structural similarity to nucleic acids. While studies on the synthesis of PPEs began in the 1970s, the scope of their use as biomaterials has increased in the last 20 years. One advantageous property of PPEs is their molecular diversity due to the presence of multivalent phosphorus in their backbones, which allows their physicochemical and biointerfacial properties to be easily controlled to produce the desired molecular platforms for functional biomaterials. Polyphosphodiesters (PPDEs) are analogs of PPEs that have recently attracted interest due to their strong affinity for biominerals. This review describes the fundamental properties of PPDEs and recent research in the field of macromolecular bone therapeutics. Full article

(This article belongs to the Special Issue Phosphorus-Containing Materials and Polymers: How a Central Element of All Living Matter can be Used in the Synthetic World)

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General structure of polyphosphodiesters (PPDEs). Full article ">Figure 2
Synthetic routes to polyphosphodiesters (PPDEs). Full article ">Figure 3
(a) Chemical structure of polyphosphoester copolymers (P(EPx/EEPy)) and (b) the effect of the phosphodiester composition of the copolymers on their mineral affinity. Full article ">Figure 4
(a) Chemical structure of the polyphosphodiester PEP·Na macromonomer and (b) scanning electron micrographs of poly(ether ether ketone) (PEEK) and poly(PEP·Na)-immobilized PEEK specimens that had been soaked in ×1.5 simulated body fluid (1.5 SBF) for 28 days. Full article ">Figure 5
(a) Chemical structure of amphophilic PPDEs. (b) Amphiphilic polyphosphodiester copolymer [CH-P(EPx/EEPy)]-immobilized 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) vesicles. Scale bar represents 500 nm. (c) Poly L-lactic acid nanoparticles bearing amphiphilic poly(ethylene sodium phosphate) (CH-PEP·Na). Scale bar represents 200 nm. (d) Bovine serum albumin/CH-PEP·Na conjugates. Scale bar represents 200 nm. Full article ">Figure 6
(a) Viability and (b) morphology of MC3T3-E1 cells following contact with poly(ethylene sodium phosphate) (PEP·Na) or poly(phosphate) (polyP). ●: PEP·Na; ●: polyP. Reproduced with permission from reference [<a href="#B33-molecules-25-00758" class="html-bibr">33</a>]. Copyright 2018 by The Royal Society of Chemistry. Full article ">Figure 7
(a) Densities of adherent osteoclasts on bovine bone slices after incubation with poly(ethylene sodium phosphate) (PEP·Na) for 24 h (n = 4). Student’s t-test was performed on the samples to test the statistical significance of differences (*p < 0.005). (b) Optical micrographs of adherent osteoclasts on a bovine bone slice after cultivation with PEP·Na for 24 h. Scale bars represent 100 μm. Reproduced with permission from reference [<a href="#B36-molecules-25-00758" class="html-bibr">36</a>]. Copyright 2015 by Wiley Interscience. Full article ">Figure 8
(a) Chemical structure of fluorescence-labeled poly(ethylene sodium phosphate) (Cy5-PEP·Na) and (b) in vivo fluorescence imaging of ICR mice at 0, 3, 30, and 75 h after the intravenous injection of Cy5-PEP·Na or Cy5-Az. Reproduced with permission from reference [<a href="#B33-molecules-25-00758" class="html-bibr">33</a>]. Copyright 2018 by The Royal Society of Chemistry. Full article ">

15 pages, 5676 KiB

Open AccessArticle

Quercetin Inhibits Cell Survival and Metastatic Ability via the EMT-Mediated Pathway in Oral Squamous Cell Carcinoma

by So Ra Kim, Eun Young Lee, Da Jeong Kim, Hye Jung Kim and Hae Ryoun Park

Molecules 2020, 25(3), 757; https://doi.org/10.3390/molecules25030757 - 10 Feb 2020

Cited by 25 | Viewed by 4603

Abstract

This study aimed to investigate whether quercetin exerts anticancer effects on oral squamous cell carcinoma (OSCC) cell lines and to elucidate its mechanism of action. These anticancer effects in OSCC cells were assessed using an MTT assay, flow cytometry (to assess the cell [...] Read more.

This study aimed to investigate whether quercetin exerts anticancer effects on oral squamous cell carcinoma (OSCC) cell lines and to elucidate its mechanism of action. These anticancer effects in OSCC cells were assessed using an MTT assay, flow cytometry (to assess the cell cycle), wound-healing assay, invasion assay, Western blot analysis, gelatin zymography, and immunofluorescence. To investigate whether quercetin also inhibits transforming growth factor β1 (TGF-β1)-induced epithelial–mesenchymal transition (EMT) in human keratinocyte cells, HaCaT cells were treated with TGF-β1. Overall, our results strongly suggest that quercetin suppressed the viability of OSCC cells by inducing cell cycle arrest at the G2/M phase. However, quercetin did not affect cell viability of human keratinocytes such as HaCaT (immortal keratinocyte) and nHOK (primary normal human oral keratinocyte) cells. Additionally, quercetin suppresses cell migration through EMT and matrix metalloproteinase (MMP) in OSCC cells and decreases TGF-β1-induced EMT in HaCaT cells. In conclusion, this study is the first, to our knowledge, to demonstrate that quercetin can inhibit the survival and metastatic ability of OSCC cells via the EMT-mediated pathway, specifically Slug. Quercetin may thus provide a novel pharmacological approach for the treatment of OSCCs. Full article

(This article belongs to the Special Issue Antitumor and Anti-HIV Agents from Natural Products)

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Quercetin reduced cell viability and arrested the G2/M phase cell cycle in oral squamous cell carcinoma (OSCC) cells. (A) Cell viability was investigated by an MTT assay. Oral squamous cell carcinoma cell lines (OSC20, SAS, and HN22 cells) were treated with quercetin (10, 20, 40, 80, and 160 μM). (B) Quercetin was shown to induce cell cycle arrest in OSC20, SAS, and HN22 cells. Data are the means ± SEM. * p < 0.05 and ** p < 0.01 vs. corresponding control (quercetin 0 μM). Full article ">Figure 2
Cell migration ability assessed by a wound-healing assay. (A) Changes in the wound area were observed after 24 h. In the quercetin-treated cells, the wound area was less closed. This indicates a decrease in migration capacity. (B) The wound area was calculated and presented as a graph. Data are the means ± SEM. * p < 0.05 and ** p < 0.01 vs. the corresponding control (quercetin 0 μM). Full article ">Figure 3
Quercetin is shown to induce regulation of epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP). (A) Western blotting was conducted to examine the changes in the EMT inducers. The results showed that the epithelial markers (E-cadherin and claudin-1) were upregulated, and the mesenchymal markers (fibronectin, vimentin, and alpha-smooth muscle actin (α-SMA)) were downregulated upon treatment with quercetin. (B) Quantitation of A. The band intensities of each target protein were measured using an image analyzer and presented as relative ratio. (C) Gelatin zymography shows the MMP-2 and MMP-9 activities in oral cancer cell lines (OSC20, SAS, and HN22 cells) upon quercetin treatment. Data are the means ± SEM. * p < 0.05, and ** p < 0.01 vs. the corresponding control (quercetin 0 μM). Full article ">Figure 4
EMT-activating transcription factors were detected using Western blot and immunofluorescence. (A) The Western blot showed that quercetin downregulated EMT transcription factors at the protein level. (B) Quantitation of A. The band intensities of each target protein were measured using an image analyzer and presented as relative ratio. (C) Representative fluorescence microscopy images of Twist in OSCC cell lines. (D) Representative fluorescence microscopy images of Slug in OSCC cell lines. Scale bars: 20 μM. Data are the means ± SEM. * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. the corresponding control (quercetin 0 μM). Full article ">Figure 5
Quercetin was not toxic in normal keratocyte and transforming growth factor β1 (TGF-β1) stimulated EMT in HaCaT cells. (A) To examine the effect of quercetin on cell viability, an MTT assay was conducted on HaCaT and nHOK cells. Data are means ± SEM. * p < 0.05 vs. the corresponding control (quercetin 0 μM). (B) Expression of EMT-related markers such as in TGF-β1-treated HaCaT cells were analyzed by Western blotting. (C–H) Quantitation of B. The band intensities of each target protein were measured using an image analyzer and presented as relative ratio. Data are means ± SEM. * p < 0.05 and *** p < 0.005 vs. corresponding control (TGF-β1 0 ng/mL). Full article ">Figure 6
Quercetin inhibited TGF-β1-induced EMT. (A) Experimental setup. (B) Western blot results showed that quercetin also regulated TGF-β1-induced EMT markers. (C) Treatment of TGF-β1 also changed the morphology of HaCaT. Further, quercetin induced morphological recovery. Scale bars: 50 μM. (D–I) Quantification of hRPTECs viability by MTT assay. (J,K) A wound-healing assay was conducted to evaluate the TGF-β1-induced EMT migration ability; quercetin attenuated EMT-induced migration in HaCaT cells. (L) Quercetin inhibited the invasion capacity of EMT-induced HaCaT cells. Data are the means ± SEM. * p < 0.05, and *** p < 0.001 vs. the corresponding control (without TGF-β1 and quercetin); # p < 0.05 vs. the corresponding control (with TGF-β1 and without quercetin). Full article ">

20 pages, 14933 KiB

Open AccessArticle

An Interpenetrating Alginate/Gelatin Network for Three-Dimensional (3D) Cell Cultures and Organ Bioprinting

by Qiuhong Chen, Xiaohong Tian, Jun Fan, Hao Tong, Qiang Ao and Xiaohong Wang

Molecules 2020, 25(3), 756; https://doi.org/10.3390/molecules25030756 - 10 Feb 2020

Cited by 54 | Viewed by 6571

Abstract

Crosslinking is an effective way to improve the physiochemical and biochemical properties of hydrogels. In this study, we describe an interpenetrating polymer network (IPN) of alginate/gelatin hydrogels (i.e., A-G-IPN) in which cells can be encapsulated for in vitro three-dimensional (3D) cultures and organ [...] Read more.

Crosslinking is an effective way to improve the physiochemical and biochemical properties of hydrogels. In this study, we describe an interpenetrating polymer network (IPN) of alginate/gelatin hydrogels (i.e., A-G-IPN) in which cells can be encapsulated for in vitro three-dimensional (3D) cultures and organ bioprinting. A double crosslinking model, i.e., using Ca²⁺ to crosslink alginate molecules and transglutaminase (TG) to crosslink gelatin molecules, is exploited to improve the physiochemical, such as water holding capacity, hardness and structural integrity, and biochemical properties, such as cytocompatibility, of the alginate/gelatin hydrogels. For the sake of convenience, the individual ionic (i.e., only treatment with Ca²⁺) or enzymatic (i.e., only treatment with TG) crosslinked alginate/gelatin hydrogels are referred as alginate-semi-IPN (i.e., A-semi-IPN) or gelatin-semi-IPN (i.e., G-semi-IPN), respectively. Tunable physiochemical and biochemical properties of the hydrogels have been obtained by changing the crosslinking sequences and polymer concentrations. Cytocompatibilities of the obtained hydrogels are evaluated through in vitro 3D cell cultures and bioprinting. The double crosslinked A-G-IPN hydrogel is a promising candidate for a wide range of biomedical applications, including bioartificial organ manufacturing, high-throughput drug screening, and pathological mechanism analyses. Full article

(This article belongs to the Special Issue Biomedical Hydrogels: Synthesis and Applications)

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15 pages, 1084 KiB

Open AccessArticle

An Optimised Di-Boronate-ChemMatrix Affinity Chromatography to Trap Deoxyfructosylated Peptides as Biomarkers of Glycation

by Monika Kijewska, Francesca Nuti, Magdalena Wierzbicka, Mateusz Waliczek, Patrycja Ledwoń, Agnieszka Staśkiewicz, Feliciana Real-Fernandez, Giuseppina Sabatino, Paolo Rovero, Piotr Stefanowicz, Zbigniew Szewczuk and Anna Maria Papini

Molecules 2020, 25(3), 755; https://doi.org/10.3390/molecules25030755 - 10 Feb 2020

Cited by 10 | Viewed by 4599

Abstract

We report herein a novel ChemMatrix^® Rink resin functionalised with two phenylboronate (PhB) moieties linked on the N-α and N-ε amino functions of a lysine residue to specifically capture deoxyfructosylated peptides, compared to differently glycosylated peptides in complex mixtures. The [...] Read more.

We report herein a novel ChemMatrix^® Rink resin functionalised with two phenylboronate (PhB) moieties linked on the N-α and N-ε amino functions of a lysine residue to specifically capture deoxyfructosylated peptides, compared to differently glycosylated peptides in complex mixtures. The new PhB-Lys(PhB)-ChemMatrix^® Rink resin allows for exploitation of the previously demonstrated ability of cis diols to form phenylboronic esters. The optimised capturing and cleavage procedure from the novel functionalised resin showed that only the peptides containing deoxyfructosyl-lysine moieties can be efficiently and specifically detected by HR-MS and MS/MS experiments. We also investigated the high-selective affinity to deoxyfructosylated peptides in an ad hoc mixture containing unique synthetic non-modified peptides and in the hydrolysates of human and bovine serum albumin as complex peptide mixtures. We demonstrated that the deoxyfructopyranosyl moiety on lysine residues is crucial in the capturing reaction. Therefore, the novel specifically-designed PhB-Lys(PhB)-ChemMatrix^® Rink resin, which has the highest affinity to deoxyfructosylated peptides, is a candidate to quantitatively separate early glycation peptides from complex mixtures to investigate their role in diabetes complications in the clinics. Full article

(This article belongs to the Section Bioorganic Chemistry)

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10 pages, 1446 KiB

Open AccessArticle

Effect of Polyvinyl Alcohol on the Rheological Properties of Cement Mortar

by Fang Liu, Baomin Wang, Yunqing Xing, Kunkun Zhang and Wei Jiang

Molecules 2020, 25(3), 754; https://doi.org/10.3390/molecules25030754 - 10 Feb 2020

Cited by 27 | Viewed by 3825

Abstract

Polyvinyl alcohol (PVA) is a kind of water-soluble polymer, which has been widely used in different industries due to its excellent mechanical and chemical properties. In this paper, the effects of polyvinyl alcohol with different hydrolysis and polymerization degrees on the rheological properties [...] Read more.

Polyvinyl alcohol (PVA) is a kind of water-soluble polymer, which has been widely used in different industries due to its excellent mechanical and chemical properties. In this paper, the effects of polyvinyl alcohol with different hydrolysis and polymerization degrees on the rheological properties of cement mortar are studied. The results show that the rheological properties of PVA-modified cement mortar can be described by the modified Bingham model. The yield stress of modified cement mortar is less than that of unmodified mortar when the degree of polymerization and the content of PVA are small. With the increase of polyvinyl alcohol content and polymerization degree, the yield stress and plastic viscosity of modified cement mortar increase sharply, which are larger than those of the unmodified cement mortar. However, the effect of hydrolysis degree of PVA on yield stress and plastic viscosity of modified cement mortar is not obvious. Full article

(This article belongs to the Special Issue Structural Mechanics of Composite Materials and Structures)

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12 pages, 2502 KiB

Open AccessArticle

Melatonin Accumulation in Sweet Cherry and Its Influence on Fruit Quality and Antioxidant Properties

by Hui Xia, Yanqiu Shen, Tian Shen, Xin Wang, Xuefeng Zhang, Peng Hu, Dong Liang, Lijin Lin, Honghong Deng, Jin Wang, Qunxian Deng and Xiulan Lv

Molecules 2020, 25(3), 753; https://doi.org/10.3390/molecules25030753 - 10 Feb 2020

Cited by 55 | Viewed by 4787

Abstract

Although the effects of melatonin on plant abiotic and biotic stress resistance have been explored in recent decades, the accumulation of endogenous melatonin in plants and its influence on fruit quality remains unclear. In the present study, melatonin accumulation levels and the expression [...] Read more.

Although the effects of melatonin on plant abiotic and biotic stress resistance have been explored in recent decades, the accumulation of endogenous melatonin in plants and its influence on fruit quality remains unclear. In the present study, melatonin accumulation levels and the expression profiles of five synthesis genes were investigated during fruit and leaf development in sweet cherry (Prunus avium L.). Melatonin was strongly accumulated in young fruits and leaves, then decreased steadily with maturation. Transcript levels of PacTDC and PacSNAT were highly correlated with melatonin content in both fruit and leaves, indicating their importance in melatonin accumulation. Furthermore, application of 50 and 100 μmol·L⁻¹ of melatonin to leaves had a greater influence on fruit quality than treatments applied to fruits, by significantly improving fruit weight, soluble solids content, and phenolic content including total phenols, flavanols, total anthocyanins, and ascorbic acid. Meanwhile, melatonin application promoted the antioxidant capacity of fruit assayed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis (3-ethylben zothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP). These results provide insights into the physiological and molecular mechanisms underlying melatonin metabolism of sweet cherry. Full article

(This article belongs to the Section Chemical Biology)

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(A) HPLC chromatogram for melatonin and its concentrations in (B) fruit and (C) leaves of Hongdeng. YL: young leaves; ML: mature leaves; OL: old leaves. Data are shown as mean ± SE with five biological replicates, different letters indicate significant differences at p < 0.05 level. Full article ">Figure 2
The transcriptional expression level of PacTDC, PacT5H1, PacT5H2, PacSNAT, and PacASMT during fruit development in Hongdeng. Data are shown as mean ± SE with three biological replicates, different letters indicate significant differences at p < 0.05 level. Full article ">Figure 3
The transcriptional expression level of PacTDC, PacT5H1, PacT5H2, PacSNAT, and PacASMT during leaf development in Hongdeng. YL: young leaves; ML: mature leaves; OL: old leaves. Data are shown as mean ± SE with three biological replicates, different letters indicate significant differences at p < 0.05 level. Full article ">Figure 4
(A) The melatonin content in fruits, and the changes of (B) fruit weight, (C) soluble solids content, and (D) titrable acid content after exogenous melatonin application in Hongdeng sweet cherry. Data are shown as mean ± SE with five biological replicates, different letters indicate significant differences at p < 0.05 level. Full article ">Figure 5
The changes of (A) total phenolics content (TPC), (B) total flavonoids content (TFC), (C) total flavanols content (TFAC), (D) total monomeric anthocyanins, (E) total ascorbic acid, and (F) ascorbic acid after exogenous melatonin application in Hongdeng sweet cherry. Data are shown as mean ± SE, with five biological replicates, different letters indicate significant differences at p < 0.05 level. Full article ">Figure 6
Antioxidant activity determined by (A) 2,2-diphenyl-1-picrylhydrazyl (DPPH), (B) 2,2′-azinobis (3-ethylben zothiazoline-6-sulfonic acid) (ABTS), and (C)ferric reducing antioxidant power (FRAP) assays of Hongdeng sweet cherry after exogenous melatonin application. Data are shown as mean ± SE, with five biological replicates, different letters indicate significant differences at p < 0.05 level. Full article ">

18 pages, 5347 KiB

Open AccessReview

Analytical Approaches for Analysis of Safety of Modern Food Packaging: A Review

by Magdalena Wrona and Cristina Nerín

Molecules 2020, 25(3), 752; https://doi.org/10.3390/molecules25030752 - 10 Feb 2020

Cited by 50 | Viewed by 8317

Abstract

Nowadays, food packaging is a crucial tool for preserving food quality and has become an inseparable part of our daily life. Strong consumer demand and market trends enforce more advanced and creative forms of food packaging. New packaging development requires safety evaluations that [...] Read more.

Nowadays, food packaging is a crucial tool for preserving food quality and has become an inseparable part of our daily life. Strong consumer demand and market trends enforce more advanced and creative forms of food packaging. New packaging development requires safety evaluations that always implicate the application of complex analytical methods. The present work reviews the development and application of new analytical methods for detection of possible food contaminants from the packaging origin on the quality and safety of fresh food. Among food contaminants migrants, set-off migrants from printing inks, polymer degradation products, and aromatic volatile compounds can be found that may compromise the safety and organoleptic properties of food. The list of possible chemical migrants is very wide and includes antioxidants, antimicrobials, intentionally added substances (IAS), non-intentionally added substances (NIAS), monomers, oligomers, and nanoparticles. All this information collected prior to the analysis will influence the type of analyzing samples and molecules (analytes) and therefore the selection of a convenient analytical method. Different analytical strategies will be discussed, including techniques for direct polymer analysis. Full article

(This article belongs to the Special Issue Food Packaging Materials)

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Dependency diagram of analytes from food contact materials and example of analytical methods that can be applied for their analysis. GC-MS—gas chromatography coupled to mass spectrometry; GC-O-MS—gas chromatography with olfactometry coupled to MS detector; APGC-Q-TOF-MSE—atmospheric pressure gas chromatography coupled to quadrupole-time of flight mass spectrometryElevated Energy; GC-Q-Orbitrap-MS—gas chromatography coupled to quadrupole-Orbitrap mass spectrometry; LTQ-Orbitrap—hybrid linear ion trap-high resolution mass spectrometry combined with mass spectrometry; Vion IMS Q-TOF-MSE—Vion ion mobility quadruple time-of-flight with MSE technology; ASAP-Q-TOF-MS—atmospheric solids analysis probe coupled to quadruple time-of-flight with MSE technology; DART-MS—direct analysis in-real-time coupled to mass detector; LESA-nESI-MS—liquid extraction surface analysis nano-electrospray mass spectrometry; FFF-ICP-MS—field-flow fractionation coupled to inductively coupled plasma mass spectrometry; SP-IC-MS—single particle mode coupled to inductively coupled plasma mass spectrometry. Full article ">Figure 2
Structures of PLA oligomers. Reproduced from [<a href="#B15-molecules-25-00752" class="html-bibr">15</a>]. Full article ">Figure 3
Bar chart of the sensory test for comparison between (a) 4 starch-based films (BP1, BP2, BP3—different starch-based polymers manufactured from starch powder provided by a Packaging Company; BP2—biopolymer manufactured from pellets provided by a Packaging Company; BP4—starch-based polymer from different origin) and (b) starch, pellets and film BP2. Reproduced from [<a href="#B49-molecules-25-00752" class="html-bibr">49</a>]. Full article ">Figure 4
Chromatograms of polypropylene sample in (a) APGC-Q-TOF-MS and (b) GC-MS. Reproduced from [<a href="#B54-molecules-25-00752" class="html-bibr">54</a>]. Full article ">Figure 5
Surface contour plots from the optimization experimental set-up: effect of time and temperature of extraction over the total area counts. Reproduced from [<a href="#B57-molecules-25-00752" class="html-bibr">57</a>]. Full article ">Figure 6
Identification of ethoxytriethylene glycol methacrylate in 50% ethanol using 15 V and 30 V cone voltages. Reproduced from [<a href="#B20-molecules-25-00752" class="html-bibr">20</a>]. Full article ">

11 pages, 4907 KiB

Open AccessArticle

Organic Salts of p-Coumaric Acid and Trans-Ferulic Acid with Aminopicolines

by Sosthene Nyomba Kamanda and Ayesha Jacobs

Molecules 2020, 25(3), 751; https://doi.org/10.3390/molecules25030751 - 10 Feb 2020

Cited by 3 | Viewed by 3313

Abstract

p-Coumaric acid (pCA) and trans-ferulic acid (TFA) were co-crystallised with 2-amino-4-picoline (2A4MP) and 2-amino-6-picoline (2A6MP) producing organic salts of (pCA⁻)(2A4MP⁺) (1), (pCA^̶ )(2A6MP⁺) (2) [...] Read more.

p-Coumaric acid (pCA) and trans-ferulic acid (TFA) were co-crystallised with 2-amino-4-picoline (2A4MP) and 2-amino-6-picoline (2A6MP) producing organic salts of (pCA⁻)(2A4MP⁺) (1), (pCA^̶ )(2A6MP⁺) (2) and (TFA^̶ )(2A4MP⁺)·(

\frac{3}{2}

H₂O) (3). For salt 3, water was included in the crystal structure fulfilling a bridging role. pCA formed a 1:1 salt with 2A4MP (Z’ = 1) and a 4:4 salt with 2A6MP (Z’ = 4). The thermal stability of the salts was determined using differential scanning calorimetry (DSC). Salt 2 had the highest thermal stability followed by salt 1 and salt 3. The salts were also characterised using Fourier transform infrared (FTIR) spectroscopy. Hirshfeld surface analysis was used to study the different intermolecular interactions in the three salts. Solvent-assisted grinding was also investigated in attempts to reproduce the salts. Full article

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28 pages, 870 KiB

Open AccessFeature PaperArticle

Assessment of the Quality of Polluted Areas in Northwest Romania Based on the Content of Elements in Different Organs of Grapevine (Vitis vinifera L.)

by Florin Dumitru Bora, Claudiu Ioan Bunea, Romeo Chira and Andrea Bunea

Molecules 2020, 25(3), 750; https://doi.org/10.3390/molecules25030750 - 9 Feb 2020

Cited by 18 | Viewed by 3204

Abstract

The purpose of this study was to evaluate the environmental quality of polluted areas near the Baia Mare Mining and Smelting Complex for future improvements the quality of the environment in polluted areas, such as the city of Baia Mare and its surroundings. [...] Read more.

The purpose of this study was to evaluate the environmental quality of polluted areas near the Baia Mare Mining and Smelting Complex for future improvements the quality of the environment in polluted areas, such as the city of Baia Mare and its surroundings. Samples of soil and organs of grapevine (Vitis vinifera L.) were collected from Baia Mare, Baia Sprie and surrounding areas (Simleul Silvaniei) and their content of Cu, Zn, Pb, Cd, Ni, Co, As, Cr, Hg were analyzed. Most soil and plant samples showed higher metal concentrations in Baia Mare and Baia Sprie areas compared to Simleul Silvaniei, exceeding the normal values. The results obtained from the translocation factors, mobility ratio, as well as from Pearson correlation study confirmed that very useful information is recorded in plant organs: root, canes, leaves and fruit. Results also indicated that Vitis vinifera L. has some highly effective strategies to tolerate heavy metal-induced stress, may also be useful as a vegetation protection barrier from considerable atmospheric pollution. At the same time, berries are safe for consumption to a large degree, which is a great advantage of this species. Full article

(This article belongs to the Special Issue Analytical Methods for Toxics Determination)

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14 pages, 697 KiB

Open AccessReview

Health Properties and Composition of Honeysuckle Berry Lonicera caerulea L. An Update on Recent Studies

by Marta Gołba, Anna Sokół-Łętowska and Alicja Z. Kucharska

Molecules 2020, 25(3), 749; https://doi.org/10.3390/molecules25030749 - 9 Feb 2020

Cited by 65 | Viewed by 7327

Abstract

Lonicera caerulea L., also known as haskap or honeysuckle berry, is a fruit commonly planted in eastern Europe, Canada and Asia. The fruit was registered as a traditional food from a third country under European Union regulations only on December 2018. It is [...] Read more.

Lonicera caerulea L., also known as haskap or honeysuckle berry, is a fruit commonly planted in eastern Europe, Canada and Asia. The fruit was registered as a traditional food from a third country under European Union regulations only on December 2018. It is resistant to cold, pests, various soil acidities and diseases. However, its attractiveness is associated mostly with its health properties. The fruit shows anticancer, anti-inflammatory, and antioxidant activity—important factors in improving health. These features result from the diverse content of phytochemicals in honeysuckle berries with high concentrations of phytocompounds, mainly hydroxycinnamic acids, hydroxybenzoic acids, flavanols, flavones, isoflavones, flavonols, flavanones and anthocyanins but also iridoids, present in the fruit in exceptional amounts. The content and health properties of the fruit were identified to be dependent on cultivar, genotype and the place of harvesting. Great potential benefits of this nutritious food are its ability to minimize the negative effects of UV radiation, diabetes mellitus and neurodegenerative diseases, and to exert hepato- and cardioprotective activity. Full article

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15 pages, 2390 KiB

Open AccessReview

Recent Advances in Copper Catalyzed Alcohol Oxidation in Homogeneous Medium

by Telma F. S. Silva and Luísa M. D. R. S. Martins

Molecules 2020, 25(3), 748; https://doi.org/10.3390/molecules25030748 - 9 Feb 2020

Cited by 44 | Viewed by 6961

Abstract

The development of sustainable processes and products through innovative catalytic materials and procedures that allow a better use of resources is undoubtedly one of the most significant issues facing researchers nowadays. Environmental and economically advanced catalytic processes for selective oxidation of alcohols are [...] Read more.

The development of sustainable processes and products through innovative catalytic materials and procedures that allow a better use of resources is undoubtedly one of the most significant issues facing researchers nowadays. Environmental and economically advanced catalytic processes for selective oxidation of alcohols are currently focused on designing new catalysts able to activate green oxidants (dioxygen or peroxides) and applying unconventional conditions of sustainable significance, like the use of microwave irradiation as an alternative energy source. This short review aims to provide an overview of the recently (2015–2020) discovered homogeneous aerobic and peroxidative oxidations of primary and secondary alcohols catalyzed by copper complexes, highlighting new catalysts with potential application in sustainable organic synthesis, with significance in academia and industry. Full article

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13 pages, 5662 KiB

Open AccessArticle

Selection of Aptamers Specific for DEHP Based on ssDNA Library Immobilized SELEX and Development of Electrochemical Impedance Spectroscopy Aptasensor

by Qi Lu, Xixia Liu, Jianjun Hou, Qiuxue Yuan, Yani Li and Sirui Chen

Molecules 2020, 25(3), 747; https://doi.org/10.3390/molecules25030747 - 9 Feb 2020

Cited by 28 | Viewed by 4327

Abstract

A selection of aptamers specific for di(2-ethylhexyl) phthalate (DEHP) and development of electrochemical impedance spectroscopy (EIS) aptasensor are described in this paper. The aptamers were selected from an immobilized ssDNA library using the systematic evolution of ligands by exponential enrichment (SELEX). The enrichment [...] Read more.

A selection of aptamers specific for di(2-ethylhexyl) phthalate (DEHP) and development of electrochemical impedance spectroscopy (EIS) aptasensor are described in this paper. The aptamers were selected from an immobilized ssDNA library using the systematic evolution of ligands by exponential enrichment (SELEX). The enrichment was monitored using real-time quantitative PCR (Q-PCR), and the aptamers were identified by high-throughput sequencing (HTS), gold nanoparticles (AuNPs) colorimetric assay, and localized surface plasmon resonance (LSPR). The EIS aptasensor was developed to detect DEHP in water samples. After eight rounds of enrichment, HTS, AuNPs colorimetric assay, and LSPR analysis indicated that four aptamers had higher binding activity, and aptamer 31 had the highest affinity (Kd = 2.26 ± 0.06 nM). The EIS aptasensor had a limit of detection (LOD) of 0.103 pg/mL with no cross-reactivity to DEHP analogs and a mean recovery of 76.07% to 141.32% for detection of DEHP in water samples. This aptamer is novel with the highest affinity and sensitivity. Full article

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20 pages, 3764 KiB

Open AccessArticle

A Novel Dimeric Exoglucanase (GH5_38): Biochemical and Structural Characterisation towards its Application in Alkyl Cellobioside Synthesis

by Mpho S. Mafa, Heinrich W. Dirr, Samkelo Malgas, Rui W. M. Krause, Konanani Rashamuse and Brett I. Pletschke

Molecules 2020, 25(3), 746; https://doi.org/10.3390/molecules25030746 - 9 Feb 2020

Cited by 5 | Viewed by 3621

Abstract

An exoglucanase (Exg-D) from the glycoside hydrolase family 5 subfamily 38 (GH5_38) was heterologously expressed and structurally and biochemically characterised at a molecular level for its application in alkyl glycoside synthesis. The purified Exg-D existed in both dimeric and monomeric forms in solution, [...] Read more.

An exoglucanase (Exg-D) from the glycoside hydrolase family 5 subfamily 38 (GH5_38) was heterologously expressed and structurally and biochemically characterised at a molecular level for its application in alkyl glycoside synthesis. The purified Exg-D existed in both dimeric and monomeric forms in solution, which showed highest activity on mixed-linked β-glucan (88.0 and 86.7 U/mg protein, respectively) and lichenin (24.5 and 23.7 U/mg protein, respectively). They displayed a broad optimum pH range from 5.5 to 7 and a temperature optimum from 40 to 60 °C. Kinetic studies demonstrated that Exg-D had a higher affinity towards β-glucan, with a K_m of 7.9 mg/mL and a k_cat of 117.2 s⁻¹, compared to lichenin which had a K_m of 21.5 mg/mL and a k_cat of 70.0 s⁻¹. The circular dichroism profile of Exg-D showed that its secondary structure consisted of 11% α-helices, 36% β-strands and 53% coils. Exg-D performed transglycosylation using p-nitrophenyl cellobioside as a glycosyl donor and several primary alcohols as acceptors to produce methyl-, ethyl- and propyl-cellobiosides. These products were identified and quantified via thin-layer chromatography (TLC) and liquid chromatography–mass spectrometry (LC-MS). We concluded that Exg-D is a novel and promising oligomeric glycoside hydrolase for the one-step synthesis of alkyl glycosides with more than one monosaccharide unit. Full article

(This article belongs to the Special Issue Green Compounds from Bio-Sources: Characterizations, Innovative Productions and Advanced Technological Applications)

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13 pages, 3300 KiB

Open AccessFeature PaperReview

The Pharmaceutical Industry in 2019. An Analysis of FDA Drug Approvals from the Perspective of Molecules

by Beatriz G. de la Torre and Fernando Albericio

Molecules 2020, 25(3), 745; https://doi.org/10.3390/molecules25030745 - 9 Feb 2020

Cited by 132 | Viewed by 13285

Abstract

During 2019, the US Food and Drug Administration (FDA) approved 48 new drugs (38 New Chemical Entities and 10 Biologics). Although this figure is slightly lower than that registered in 2018 (59 divided between 42 New Chemical Entities and 17 Biologics), a year [...] Read more.

During 2019, the US Food and Drug Administration (FDA) approved 48 new drugs (38 New Chemical Entities and 10 Biologics). Although this figure is slightly lower than that registered in 2018 (59 divided between 42 New Chemical Entities and 17 Biologics), a year that broke a record with respect to new drugs approved by this agency, it builds on the trend initiated in 2017, when 46 drugs were approved. Of note, three antibody drug conjugates, three peptides, and two oligonucleotides were approved in 2019. This report analyzes the 48 new drugs of the class of 2019 from a strictly chemical perspective. The classification, which was carried out on the basis of chemical structure, includes the following: Biologics (antibody drug conjugates, antibodies, and proteins); TIDES (peptide and oligonucleotides); drug combinations; natural products; and small molecules. Full article

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14 pages, 2476 KiB

Open AccessArticle

Identification and Characterization of Nematicidal Volatile Organic Compounds from Deep-Sea Virgibacillus dokdonensis MCCC 1A00493

by Dian Huang, Chen Yu, Zongze Shao, Minmin Cai, Guangyu Li, Longyu Zheng, Ziniu Yu and Jibin Zhang

Molecules 2020, 25(3), 744; https://doi.org/10.3390/molecules25030744 - 9 Feb 2020

Cited by 35 | Viewed by 3924

Abstract

Root-knot nematode diseases cause severe yield and economic losses each year in global agricultural production. Virgibacillus dokdonensis MCCC 1A00493, a deep-sea bacterium, shows a significant nematicidal activity against Meloidogyne incognita in vitro. However, information about the active substances of V. dokdonensis MCCC 1A00493 [...] Read more.

Root-knot nematode diseases cause severe yield and economic losses each year in global agricultural production. Virgibacillus dokdonensis MCCC 1A00493, a deep-sea bacterium, shows a significant nematicidal activity against Meloidogyne incognita in vitro. However, information about the active substances of V. dokdonensis MCCC 1A00493 is limited. In this study, volatile organic compounds (VOCs) from V. dokdonensis MCCC 1A00493 were isolated and analyzed through solid-phase microextraction and gas chromatography–mass spectrometry. Four VOCs, namely, acetaldehyde, dimethyl disulfide, ethylbenzene, and 2-butanone, were identified, and their nematicidal activities were evaluated. The four VOCs had a variety of active modes on M. incognita juveniles. Acetaldehyde had direct contact killing, fumigation, and attraction activities; dimethyl disulfide had direct contact killing and attraction activities; ethylbenzene had an attraction activity; and 2-butanone had a repellent activity. Only acetaldehyde had a fumigant activity to inhibit egg hatching. Combining this fumigant activity against eggs and juveniles could be an effective strategy to control the different developmental stages of M. incognita. The combination of direct contact and attraction activities could also establish trapping and killing strategies against root-knot nematodes. Considering all nematicidal modes or strategies, we could use V. dokdonensis MCCC 1A00493 to set up an integrated strategy to control root-knot nematodes. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 4297 KiB

Open AccessArticle

Temperature Effect on the Adsorption and Volumetric Properties of Aqueous Solutions of Kolliphor^®ELP

by Katarzyna Szymczyk, Magdalena Szaniawska and Joanna Krawczyk

Molecules 2020, 25(3), 743; https://doi.org/10.3390/molecules25030743 - 9 Feb 2020

Cited by 6 | Viewed by 3292

Abstract

Density, viscosity and surface tension of Kolliphor^® ELP, the nonionic surfactant aqueous solutions were measured at temperature T = 293–318 K and at 5K interval. Steady-state fluorescence measurements have been also made using pyrene as a probe. On the basis of the [...] Read more.

Density, viscosity and surface tension of Kolliphor^® ELP, the nonionic surfactant aqueous solutions were measured at temperature T = 293–318 K and at 5K interval. Steady-state fluorescence measurements have been also made using pyrene as a probe. On the basis of the obtained results, a number of thermodynamic, thermo-acoustic and anharmonic parameters of the studied surfactant have been evaluated and interpreted in terms of structural effects and solute–solvent interactions. The results suggest that the molecules of studied surfactant at concentrations higher than the critical micelle concentration act as structure makers of the water structure. Full article

(This article belongs to the Section Physical Chemistry)

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22 pages, 5337 KiB

Open AccessArticle

Sterically Stabilised Polymeric Mesoporous Silica Nanoparticles Improve Doxorubicin Efficiency: Tailored Cancer Therapy

by Thashini Moodley and Moganavelli Singh

Molecules 2020, 25(3), 742; https://doi.org/10.3390/molecules25030742 - 8 Feb 2020

Cited by 27 | Viewed by 4613

Abstract

The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are [...] Read more.

The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are attractive nanocarriers due to their biodegradable, biocompatible, and relative malleable porous frameworks that can be functionalized for enhanced targeting and delivery in a variety of disease models. The optimal formulation of an MSN with polyethylene glycol (2% and 5%) and chitosan was undertaken, to produce sterically stabilized, hydrophilic MSNs, capable of efficient loading and delivery of the hydrophobic anti-neoplastic drug, doxorubicin (DOX). The pH-sensitive release kinetics of DOX, together with the anticancer, apoptosis and cell-cycle activities of DOX-loaded MSNs in selected cancer cell lines were evaluated. MSNs of 36–60 nm in size, with a pore diameter of 9.8 nm, and a cumulative surface area of 710.36 m²/g were produced. The 2% pegylated MSN formulation (PCMSN) had the highest DOX loading capacity (0.98 mg_dox/mg_msn), and a sustained release profile over 72 h. Pegylated-drug nanoconjugates were effective at a concentration range between 20–50 μg/mL, inducing apoptosis in cancer cells, and affirming their potential as effective drug delivery vehicles. Full article

(This article belongs to the Special Issue Applications of Materials in Drug Delivery)

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20 pages, 2807 KiB

Open AccessArticle

Synthesis, Structural, and Cytotoxic Properties of New Water-Soluble Copper(II) Complexes Based on 2,9-Dimethyl-1,10-Phenanthroline and Their One Derivative Containing 1,3,5-Triaza-7-Phosphaadamantane-7-Oxide

by Ewelina I. Śliwa, Urszula Śliwińska-Hill, Barbara Bażanów, Miłosz Siczek, Julia Kłak and Piotr Smoleński

Molecules 2020, 25(3), 741; https://doi.org/10.3390/molecules25030741 - 8 Feb 2020

Cited by 12 | Viewed by 4453

Abstract

A series of water-soluble copper(II) complexes based on 2,9-dimethyl-1,10-phenanthroline (dmphen) and mixed-ligands, containing PTA=O (1,3,5-triaza-7-phosphaadamantane-7-oxide) have been synthesized and fully characterized. Two types of complexes have been obtained, monocationic [Cu(NO₃)(O-PTA=O)(dmphen)][PF₆] (1), [Cu(Cl)(dmphen)₂][PF₆] ( [...] Read more.

A series of water-soluble copper(II) complexes based on 2,9-dimethyl-1,10-phenanthroline (dmphen) and mixed-ligands, containing PTA=O (1,3,5-triaza-7-phosphaadamantane-7-oxide) have been synthesized and fully characterized. Two types of complexes have been obtained, monocationic [Cu(NO₃)(O-PTA=O)(dmphen)][PF₆] (1), [Cu(Cl)(dmphen)₂][PF₆] (2), and neutral [Cu(NO₃)₂(dmphen)] (3). The solid-state structures of all complexes have been determined by single-crystal X-ray diffraction. Magnetic studies for the complex 1–3 indicated a very weak antiferromagnetic interaction between copper(II) ions in crystal lattice. Complexes were successfully evaluated for their cytotoxic activities on the normal human dermal fibroblast (NHDF) cell line and the antitumor activity using the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa), colon (LoVo), and breast adenocarcinoma (MCF-7) cell lines. Complexes 1 and 3 revealed lower toxicity to NHDF than A549 and HeLa cells, meanwhile compound 2 appeared to be more toxic to NHDF cell line in comparison to all cancer lines. Additionally, interactions between the complexes and human apo-transferrin (apo-Tf) using fluorescence and circular dichroism (CD) spectroscopy were also investigated. All compounds interacted with apo-transferrin, causing same changes of the protein conformation. Electrostatic interactions dominate in the 1/2 – apo- Tf systems and hydrophobic and ionic interactions in the case of 3. Full article

(This article belongs to the Special Issue Bipyridines: Synthesis, Functionalization and Applications)

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Full article ">Figure 1
Molecular structure of compound 1. Ellipsoids shown at the 50% probability. Color code: Grey, carbon; blue, nitrogen; red, oxygen; violet, phosphor; green, fluoride; cyan, copper; light grey, hydrogen. Selected bond lengths [Å] and angles [°]: Cu-N21, 1.972(1); Cu-N11, 1.995(1); Cu-O12, 2.102(1); Cu-O13, 2.028(1); Cu-O23, 2.083(1); P12-O12,1.506(1); N11-Cu-N21, 84.66(5); Cu-N11-C11, 130.80(9); Cu-O12-P12, 134.23(7); N11-Cu-O12, 112.83(4); N11-Cu-O13, 102.90(5); N11-Cu-O23, 148.04(5); N11-Cu-O12, 100.93(5); N21-Cu-O13, 161.17(5); N21-Cu-O23, 101.54(5); N21-Cu-O13, 92.08(4); O12-Cu-O23, 96.90(5); O13-Cu-O23, 63.04(5). Full article ">Figure 2
Molecular structure of compound 3 with atom labelling scheme. Ellipsoids shown at the 50% probability. Color code: Grey, carbon; blue, nitrogen; red, oxygen; cyan, copper; light grey, hydrogen. Selected bond lengths (Å) and angles (°): Cu-O12, 2.42; Cu-O22, 2.006; Cu-N11, 1.989; O12-Cu-O22, 57.62; O12-Cu-N11, 96.32; O12-Cu-N11, 119.68; O12-Cu-O12, 131.58; O12-Cu-O22, 87.13; O22-Cu-N11, 152.35; O22-Cu-N11, 99.67; O22-Cu-O22, 88.88; N11-Cu-N11, 84.89; N11-Cu-O22, 99.67. Full article ">Figure 3
The π-π stacking interactions represented in red dashed line in compound 1 (A) and compound 3 (B). Full article ">Figure 4
Temperature dependences of experimental χmT vs. T (χm per one CuII atom) for 1–3. The solid lines are the calculated curves derived from Equations (1) and (2). The inset shows field dependences of the magnetization (M per one CuII atom) at 2 K for 1–3. The solid line is the Brillouin function curve for one uncoupled spin with S = 1/2 and g = 2.0. Full article ">Figure 5
Fluorescence emission spectra of apo-Tf - 3 systems under physiological conditions (Phosphate-Buffered Saline-PBS, pH = 7.40, T = 310K), λex = 280 nm, Capo-Tf = 2·10−6M. Full article ">Figure 6
Modified Stern–Volmer (A) and log((F0 – F)/F) vs. log(Q) (B) plots of the apo-Tf- 3 system at 300 K and 310 K (PBS, pH = 7.40, λex = 280nm). Full article ">Figure 7
Circular dichroism -CD spectra of apo-Tf – 3 systems under physiological conditions (PBS, pH = 7.40, T = 310 K) (Capo-Tf = 5 × 10−6 M). Full article ">Scheme 1
Structural formulas of the ligands. Full article ">Scheme 2
Schematic representation of the synthesis and structural formulae for 1–3. Full article ">

15 pages, 7672 KiB

Open AccessArticle

Ultrasound and Radiation-Induced Catalytic Oxidation of 1-Phenylethanol to Acetophenone with Iron-Containing Particulate Catalysts

by Mohamed M. A. Soliman, Maximilian N. Kopylovich, Elisabete C. B. A. Alegria, Ana P. C. Ribeiro, Ana M. Ferraria, Ana M. Botelho do Rego, Luís M. M. Correia, Marta S. Saraiva and Armando J. L. Pombeiro

Molecules 2020, 25(3), 740; https://doi.org/10.3390/molecules25030740 - 8 Feb 2020

Cited by 6 | Viewed by 3686

Abstract

Iron-containing particulate catalysts of 0.1–1 µm size were prepared by wet and ball-milling procedures from common salts and characterized by FTIR, TGA, UV-Vis, PXRD, FEG-SEM, and XPS analyses. It was found that when the wet method was used, semi-spherical magnetic nanoparticles were formed, [...] Read more.

Iron-containing particulate catalysts of 0.1–1 µm size were prepared by wet and ball-milling procedures from common salts and characterized by FTIR, TGA, UV-Vis, PXRD, FEG-SEM, and XPS analyses. It was found that when the wet method was used, semi-spherical magnetic nanoparticles were formed, whereas the mechanochemical method resulted in the formation of nonmagnetic microscale needles and rectangles. Catalytic activity of the prepared materials in the oxidation of 1-phenylethanol to acetophenone was assessed under conventional heating, microwave (MW) irradiation, ultrasound (US), and oscillating magnetic field of high frequency (induction heating). In general, the catalysts obtained by wet methods exhibit lower activities, whereas the materials prepared by ball milling afford better acetophenone yields (up to 83%). A significant increase in yield (up to 4 times) was observed under the induction heating if compared to conventional heating. The study demonstrated that MW, US irradiations, and induction heating may have great potential as alternative ways to activate the catalytic system for alcohol oxidation. The possibility of the synthesized material to be magnetically recoverable has been also verified. Full article

(This article belongs to the Special Issue Mechanically Responsive Materials and Their Applications)

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20 pages, 3259 KiB

Open AccessArticle

Towards an Understanding of the Mode of Action of Human Aromatase Activity for Azoles through Quantum Chemical Descriptors-Based Regression and Structure Activity Relationship Modeling Analysis

by Chayawan Chayawan, Cosimo Toma, Emilio Benfenati and Ana Y. Caballero Alfonso

Molecules 2020, 25(3), 739; https://doi.org/10.3390/molecules25030739 - 8 Feb 2020

Cited by 8 | Viewed by 4915

Abstract

Aromatase is an enzyme member of the cytochrome P450 superfamily coded by the CYP19A1 gene. Its main action is the conversion of androgens into estrogens, transforming androstenedione into estrone and testosterone into estradiol. This enzyme is present in several tissues and it has [...] Read more.

Aromatase is an enzyme member of the cytochrome P450 superfamily coded by the CYP19A1 gene. Its main action is the conversion of androgens into estrogens, transforming androstenedione into estrone and testosterone into estradiol. This enzyme is present in several tissues and it has a key role in the maintenance of the balance of androgens and estrogens, and therefore in the regulation of the endocrine system. With regard to chemical safety and human health, azoles, which are used as agrochemicals and pharmaceuticals, are potential endocrine disruptors due to their agonist or antagonist interactions with the human aromatase enzyme. This theoretical study investigated the active agonist and antagonist properties of “chemical classes of azoles” to determine the relationships of azole interaction with CYP19A1, using stereochemical and electronic properties of the molecules through classification and multilinear regression (MLR) modeling. The antagonist activities for the same substituent on diazoles and triazoles vary with its chemical composition and its position and both heterocyclic systems require aromatic substituents. The triazoles require the spherical shape and diazoles have to be in proper proportion of the branching index and the number of ring systems for the inhibition. Considering the electronic aspects, triazole antagonist activity depends on the electrophilicity index that originates from interelectronic exchange interaction (ω_HF) and the LUMO energy (

E_{LUMO}^{PM 7}

), and the diazole antagonist activity originates from the penultimate orbital (

E_{HOMONL}^{PM 7}

) of diazoles. The regression models for agonist activity show that it is opposed by the static charges but favored by the delocalized charges on the diazoles and thiazoles. This study proposes that the electron penetration of azoles toward heme group decides the binding behavior and stereochemistry requirement for antagonist activity against CYP19A1 enzyme. Full article

(This article belongs to the Special Issue Integrated QSAR)

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16 pages, 1174 KiB

Open AccessReview

Current Approaches to and Future Perspectives on Methomyl Degradation in Contaminated Soil/Water Environments

by Ziqiu Lin, Wenping Zhang, Shimei Pang, Yaohua Huang, Sandhya Mishra, Pankaj Bhatt and Shaohua Chen

Molecules 2020, 25(3), 738; https://doi.org/10.3390/molecules25030738 - 8 Feb 2020

Cited by 57 | Viewed by 6649

Abstract

Methomyl is a broad-spectrum oxime carbamate commonly used to control arthropods, nematodes, flies, and crop pests. However, extensive use of this pesticide in agricultural practices has led to environmental toxicity and human health issues. Oxidation, incineration, adsorption, and microbial degradation methods have been [...] Read more.

Methomyl is a broad-spectrum oxime carbamate commonly used to control arthropods, nematodes, flies, and crop pests. However, extensive use of this pesticide in agricultural practices has led to environmental toxicity and human health issues. Oxidation, incineration, adsorption, and microbial degradation methods have been developed to remove insecticidal residues from soil/water environments. Compared with physicochemical methods, biodegradation is considered to be a cost-effective and ecofriendly approach to the removal of pesticide residues. Therefore, micro-organisms have become a key component of the degradation and detoxification of methomyl through catabolic pathways and genetic determinants. Several species of methomyl-degrading bacteria have been isolated and characterized, including Paracoccus, Pseudomonas, Aminobacter, Flavobacterium, Alcaligenes, Bacillus, Serratia, Novosphingobium, and Trametes. The degradation pathways of methomyl and the fate of several metabolites have been investigated. Further in-depth studies based on molecular biology and genetics are needed to elaborate their role in the evolution of novel catabolic pathways and the microbial degradation of methomyl. In this review, we highlight the mechanism of microbial degradation of methomyl along with metabolic pathways and genes/enzymes of different genera. Full article

(This article belongs to the Special Issue Biodegradation of Conventional and Emerging Pollutants)

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20 pages, 4197 KiB

Open AccessFeature PaperReview

Spider Silk for Tissue Engineering Applications

by Sahar Salehi, Kim Koeck and Thomas Scheibel

Molecules 2020, 25(3), 737; https://doi.org/10.3390/molecules25030737 - 8 Feb 2020

Cited by 135 | Viewed by 19415

Abstract

Due to its properties, such as biodegradability, low density, excellent biocompatibility and unique mechanics, spider silk has been used as a natural biomaterial for a myriad of applications. First clinical applications of spider silk as suture material go back to the 18th century. [...] Read more.

Due to its properties, such as biodegradability, low density, excellent biocompatibility and unique mechanics, spider silk has been used as a natural biomaterial for a myriad of applications. First clinical applications of spider silk as suture material go back to the 18th century. Nowadays, since natural production using spiders is limited due to problems with farming spiders, recombinant production of spider silk proteins seems to be the best way to produce material in sufficient quantities. The availability of recombinantly produced spider silk proteins, as well as their good processability has opened the path towards modern biomedical applications. Here, we highlight the research on spider silk-based materials in the field of tissue engineering and summarize various two-dimensional (2D) and three-dimensional (3D) scaffolds made of spider silk. Finally, different applications of spider silk-based materials are reviewed in the field of tissue engineering in vitro and in vivo. Full article

(This article belongs to the Special Issue Silk Fibroin Materials)

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18 pages, 4445 KiB

Open AccessArticle

Smart, Tunable CQDs with Antioxidant Properties for Biomedical Applications—Ecofriendly Synthesis and Characterization

by Łukasz Janus, Julia Radwan-Pragłowska, Marek Piątkowski and Dariusz Bogdał

Molecules 2020, 25(3), 736; https://doi.org/10.3390/molecules25030736 - 8 Feb 2020

Cited by 20 | Viewed by 3813

Abstract

Carbon quantum dots (CQDs) are nanoobjects of a size below 10 nm. Due to their favorable features, such as tunable luminescence, unique optical properties, water solubility, and lack of cytotoxicity, they are willingly applied in biomedicine. They can be obtained via bottom-up and [...] Read more.

Carbon quantum dots (CQDs) are nanoobjects of a size below 10 nm. Due to their favorable features, such as tunable luminescence, unique optical properties, water solubility, and lack of cytotoxicity, they are willingly applied in biomedicine. They can be obtained via bottom-up and top-down methods. However, to increase their quantum yield they must undergo post-processing. The aim of the following research was to obtain a new type of CQDs modified with a rhodamine b derivative to enhance their fluorescence performance without biocompability deterioration. For their preparation glucose was used as a precursor and four different carbonizing agents which affected semi- and final products luminescence properties. The ready nanomaterials were investigated over their chemical structure by FTIR and NMR, whereas morphology was investigated by the TEM method. Their optical properties were determined by UV–VIS spectroscopy. Fluorescence behavior, photo- and pH-stability, as well as solvatochromism showed their applicability in various biomedical applications due to the controlled properties. The samples exhibited excellent antioxidant activity and lack of cytotoxicity on L929 mouse fibroblasts. The results showed that proposed strategy enables preparation of the superior nanomaterials with outstanding luminescence properties such as quantum yield up to 17% which can be successfully applied in cell labelling, bioimaging, and theranostics. Full article

(This article belongs to the Special Issue Carbon Dots—Promising Nanomaterials)

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21 pages, 1115 KiB

Open AccessReview

Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair

by Nicholas G. Economos, Stanley Oyaghire, Elias Quijano, Adele S. Ricciardi, W. Mark Saltzman and Peter M. Glazer

Molecules 2020, 25(3), 735; https://doi.org/10.3390/molecules25030735 - 8 Feb 2020

Cited by 44 | Viewed by 7866

Abstract

Unusual nucleic acid structures are salient triggers of endogenous repair and can occur in sequence-specific contexts. Peptide nucleic acids (PNAs) rely on these principles to achieve non-enzymatic gene editing. By forming high-affinity heterotriplex structures within the genome, PNAs have been used to correct [...] Read more.

Unusual nucleic acid structures are salient triggers of endogenous repair and can occur in sequence-specific contexts. Peptide nucleic acids (PNAs) rely on these principles to achieve non-enzymatic gene editing. By forming high-affinity heterotriplex structures within the genome, PNAs have been used to correct multiple human disease-relevant mutations with low off-target effects. Advances in molecular design, chemical modification, and delivery have enabled systemic in vivo application of PNAs resulting in detectable editing in preclinical mouse models. In a model of β-thalassemia, treated animals demonstrated clinically relevant protein restoration and disease phenotype amelioration, suggesting a potential for curative therapeutic application of PNAs to monogenic disorders. This review discusses the rationale and advances of PNA technologies and their application to gene editing with an emphasis on structural biochemistry and repair. Full article

(This article belongs to the Special Issue Peptide Nucleic Acids: Applications in Biomedical Sciences)

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