In this study, the antileishmanial and cytotoxic activities of secondary metabolites isolated from Tabernaemontana ventricosa Hochst. ex A. DC., Aloe tororoana Reynolds, and Aloe schweinfurthii var. labworana Reynolds were investigated.... more
In this study, the antileishmanial and cytotoxic activities of secondary metabolites isolated from Tabernaemontana ventricosa Hochst. ex A. DC., Aloe tororoana Reynolds, and Aloe schweinfurthii var. labworana Reynolds were investigated. Overall, nineteen known compounds were isolated from the three plant species. The compounds were characterized based on their spectroscopic data. Voacristine and aloenin were the most active compounds against promastigotes of antimony-sensitive Leishmania donovani (IC50 11 ± 5.2 μM and 26 ± 6.5 µM, respectively) with low toxicity against RAW264.7, murine monocyte/macrophage-like cells. The in silico docking evaluation and in vitro NO generation assay also substantially support the antileishmanial effects of these compounds. In a cytotoxicity assay against cancer and normal cell lines, ursolic acid highly inhibited proliferation of lung cancer cells, A549 (IC50 6.61 ± 0.7 μM) while voacristine was moderately active against human liver cancer cells, He...
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Most of the tropical neglected diseases casing agents are single celled eukaryotic parasites that affect millions of global populations physiologically, economically and sociologically. These diseases not only affect humans but also... more
Most of the tropical neglected diseases casing agents are single celled eukaryotic parasites that affect millions of global populations physiologically, economically and sociologically. These diseases not only affect humans but also affect the animals that sustain life within these populations completely influencing the societal fabric on sustenance. The current therapies are limited to poorly selected drugs that have a poor efficacy and extreme adverse effects. The current quick growth in sequencing and atomic structure determination of the parasites cellular organelles has accelerated the venture to obtain newer intervenes that would serve to benefit these populations. The rapid in silico determination of the ribosomal structure, specifically the 18S rRNA has revealed the mechanisms by which some therapeutics induces their effect on the process of translation to the parasites. We show some in silico atomic resolution structures of 18S rRNA of neglected tropical diseases. We furthe...
A new flavanonol, 3-hydroxyerythrisenegalone (1), and four known compounds (2-5) were isolated from the extract of Mundulea sericea leaves. Investigation of the roots of this plant afforded an additional three known compounds (6-8). The... more
A new flavanonol, 3-hydroxyerythrisenegalone (1), and four known compounds (2-5) were isolated from the extract of Mundulea sericea leaves. Investigation of the roots of this plant afforded an additional three known compounds (6-8). The structures were elucidated using NMR spectroscopic and mass spectrometric analyses. The absolute configuration of 1 was established using ECD spectroscopy. In an antiplasmodial activity assay, compound 1 showed good activity with an IC 50 of 2.0 μM against chloroquine-resistant W2, and 6.6 μM against the chloro-quine-sensitive 3D7 strains of Plasmodium falciparum. Some of the compounds were also tested for antileishma-nial activity. Dehydrolupinifolinol (2) and sericetin (5) were active against drug-sensitive Leishmania donovani (MHOM/IN/83/AG83) with IC 50 values of 9.0 and 5.0 μM, respectively. In a cytotoxicity assay, erythrisenega-lone (3) showed significant activity on BEAS-2B (IC 50 4.9 μM) and to HePG2 (IC 50 10.8 μM) human cell lines. All the...
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Phytochemical analysis of a methanol-dichloromethane (1:1) extract of the aerial parts of Tephrosialinearis led to the isolation of 18 compounds. Seven of these, namely, lineaflavones A-D (1-4), 6-methoxygeraldone (5), 8″-acetylobovatin... more
Phytochemical analysis of a methanol-dichloromethane (1:1) extract of the aerial parts of Tephrosialinearis led to the isolation of 18 compounds. Seven of these, namely, lineaflavones A-D (1-4), 6-methoxygeraldone (5), 8″-acetylobovatin (6), and 5-hydroxy-7-methoxysaniculamin A (7) are new compounds. The compounds were characterized based on their NMR and HRMSn data. The anti-inflammatory effects of the crude extract and isolated compounds were evaluated by measuring the levels of interleukins (IL-1β, IL-2, and IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). The crude extract inhibited the release of all cytokines except IL-1β, which slightly increased in comparison to the LPS control. All the tested compounds suppressed the production of IL-2, GM-CSF, and TNF-α. Whereas compounds 1, 2, 4-8, 10-15, 17, and 18 decreased production of IL-6, compounds 1, 2, 4, 7, 10, 13-15, and 17 inhibited the release of IL-1β. It is worth noting that most of the compounds tested showed a superior reduction in cytokines release compared to the reference drug ibuprofen.
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The development of novel anti-infectives against Kinetoplastids pathogens targeting proteins is a big problem occasioned by the antigenic variation in these parasites. This is also a global concern due to the zoonosis of these parasites,... more
The development of novel anti-infectives against Kinetoplastids pathogens targeting proteins is a big problem occasioned by the antigenic variation in these parasites. This is also a global concern due to the zoonosis of these parasites, as they infect both humans and animals. Therefore, we need not only to create novel antibiotics, but also to speed up the development pipeline for these antibiotics. This may be achieved by using novel drug targets for Kinetoplastids drug discovery. In this study, we focused our attention on motifs of rRNA molecules that have been created using homology modeling. The RNA is the most ambiguous biopolymer in the kinetoplatid, which carries many different functions. For instance, tRNAs, rRNAs, and mRNAs are essential for gene expression both in the pro-and eukaryotes. However, all these types of RNAs have sequences with unique 3D structures that are specific for kinetoplastids only and can be used to shut down essential biochemical processes in kinetop...
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β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic... more
β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used to encapsulate β-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. β-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (β-Sit-PLGA and β-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. β-Sit-PLGA and β-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0 ± 29...
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Chromatographic separation of the extract of the roots of Dorstenia kameruniana (family Moraceae) led to the isolation of three new benzylbenzofuran derivatives, 2-(p-hydroxybenzyl)benzofuran-6-ol (1),... more
Chromatographic separation of the extract of the roots of Dorstenia kameruniana (family Moraceae) led to the isolation of three new benzylbenzofuran derivatives, 2-(p-hydroxybenzyl)benzofuran-6-ol (1), 2-(p-hydroxybenzyl)-7-methoxybenzofuran-6-ol (2) and 2-(p-hydroxy)-3-(3-methylbut-2-en-1-yl)benzyl)benzofuran-6-ol(3) (named dorsmerunin A, B and C, respectively), along with the known furanocoumarin, bergapten (4). The twigs of Dorstenia kameruniana also produced compounds 1-4 as well as the known chalcone licoagrochalcone A (5). The structures were elucidated by NMR spectroscopy and mass spectrometry. The isolated compounds displayed cytotoxicity against the sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells, where compounds 4 and 5 had the highest activities (IC values of 7.17 μM and 5.16 μM, respectively) against CCRF-CEM leukemia cells. Compound 5 also showed cytotoxicity against 7 sensitive or drug-resistant solid tumor cell lines (breast carcinoma, colon carc...
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Page 1. Current Organic Chemistry, 2002, 6, 365-391 365 1385-2728/02 $35.00+.00 © 2002 Bentham Science Publishers Ltd. The Preparation and Biological Significance of Phytosphingosines Amy R. Howell* and Albert J. Ndakala ...
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A general synthesis of 1,5-dioxaspiro[3.2]hexanes is described. This was accomplished via epoxidation of 2-methyleneoxetanes with dry dimethyldioxirane. A study on the chemoselectivity of the epoxidation of the double bond of... more
A general synthesis of 1,5-dioxaspiro[3.2]hexanes is described. This was accomplished via epoxidation of 2-methyleneoxetanes with dry dimethyldioxirane. A study on the chemoselectivity of the epoxidation of the double bond of 2-methyleneoxetanes against that of an isolated alkene was undertaken and resulted in the exclusive epoxidation of the enol ether double bond. The efficient access to 1,5-dioxaspiro[3.2]hexanes afforded us the opportunity of exploring the reactivity of these systems. Studies on their ring opening reactions with nucleophiles revealed an interesting dichotomy in reactivity. Most of the nucleophiles employed provided α-substituted, β ' -hydroxyketones in good yields. However, those nucleophiles that incorporated a Lewis acid produced 2,2-disubstituted oxetanes. We were intrigued by the potential application of sequences derived from the mode of ring opening leading to α-substituted, β' -hydroxyketones. The ease of manipulation of products of this reaction ...
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Page 1. Current Organic Chemistry, 2002, 6, 365-391 365 1385-2728/02 $35.00+.00 © 2002 Bentham Science Publishers Ltd. The Preparation and Biological Significance of Phytosphingosines Amy R. Howell* and Albert J. Ndakala ...
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3-Alkylidene-2-methyleneoxetanes have been prepared by treating α-alkylidene-β-lactones, derived from Morita-Baylis-Hillman-type adducts, with dimethyltitanocene. Preliminary studies of the reactivity of these little known, strained... more
3-Alkylidene-2-methyleneoxetanes have been prepared by treating α-alkylidene-β-lactones, derived from Morita-Baylis-Hillman-type adducts, with dimethyltitanocene. Preliminary studies of the reactivity of these little known, strained heterocycles are also described.