Acquired immunodeficiency syndrome (AIDS), one of the deadliest global diseases, is caused by the... more Acquired immunodeficiency syndrome (AIDS), one of the deadliest global diseases, is caused by the Human Immunodeficiency Virus (HIV). To date, there are no known conventional drugs that can cure HIV/AIDS, and this has prompted continuous scientific efforts in the search for novel and potent anti-HIV therapies. In this study, molecular dynamics simulation (MDS) and computational techniques were employed to investigate the inhibitory potential of bioactive compounds from selected South African indigenous plants against HIV-1 subtype C protease (HIVpro). Of the eight compounds (CMG, MA, UA, CA, BA, UAA, OAA and OA) evaluated, only six (CMG (−9.9 kcal/mol), MA (−9.3 kcal/mol), CA (−9.0 kcal/mol), BA (−8.3 kcal/mol), UAA (−8.5 kcal/mol), and OA (−8.6 kcal/mol)) showed favourable activities against HIVpro and binding landscapes like the reference FDA-approved drugs, Lopinavir (LPV) and Darunavir (DRV), with CMG and MA having the highest binding affinities. Using the structural analysis (r...
African Journal of Microbiology Research, Nov 16, 2011
ABSTRACT Phytochemical investigation of Eucalyptus grandis, a plant with many industrial and trad... more ABSTRACT Phytochemical investigation of Eucalyptus grandis, a plant with many industrial and traditional applications, led to the isolation of 3β-hydroxyurs-2-en-28-oic acid (FJ-2) and the synthesis of 3β-acetylurs-12-en-28-oic acid (FJ-6), with antiplatelet aggregation activity. Platelet aggregation was induced by thrombin a platelet protease-activated receptors subtype I and IV, adenosine diphosphate (ADP) a potent agonist to platelet G protein-coupled P2Y receptor and epinephrine. The results showed FJ-2 had the highest percentage inhibition (87.8 ± 1.81) which was observed to be significantly (P < 0.05) higher than the standards heparin (65.9 ± 0.91) and aspirin (65.4 ± 0.8) at a concentration of 1.0 mg/ml, using thrombin-as agonist. But this percentage inhibition was observed to decrease with increase in the concentration of FJ-2; this implied an optimal concentration (≤ 1.0 mg/ml) for inhibition of platelet aggregation by FJ-2, above which inhibition decreases. FJ-6 showed a dose dependent increase in percentage inhibition (51.4 ± 0.65 at 1.0 mg/ml and 73.8 ± 1.72 at 10 mg/ml). The two compounds differ only in their functionality but behave differently towards platelet aggregation inhibition. This preliminary result suggests that FJ-2 and FJ-6 may be taken as candidate lead natural compounds to be considered in the search for natural products with beneficial effects on aberrant platelet activation mediated cardiovascular disorders.
Leptospermum petersonii (family Myrtaceae) is often cultivated for ornamental purposes but also s... more Leptospermum petersonii (family Myrtaceae) is often cultivated for ornamental purposes but also serves as a rich source of bioactive essential oils. While several studies focused on the activities of the essential oils, this study analysed the potential of spent L. petersonii leaves as a natural food preservative. Method: We investigated the in vitro antioxidant and antimicrobial activities of crude L. petersonii extracts against activities of the purified isolated flavonoid, 6-methyltectochrysin, which was characterized using spectroscopic methods. The antioxidant assays followed ORAC, FRAP and TEAC tests. The antimicrobial activities of the extract and purified flavonoid were analysed against six multi-drug resistant microbial strains in broth dilution assays. Result: The results revealed that both the crude extracts and isolated 6-methyltectochrysin exhibited positive radical ion scavenging antioxidant potential, however the crude extract was about 6-fold more potent antioxidant ...
A group of bioactive compounds known as triterpenoids, which are often found in plant materials, ... more A group of bioactive compounds known as triterpenoids, which are often found in plant materials, have been tested to possess nutritional and pharmaceutical activity. These plant components are referred to as nutraceuticals, and are used as therapeutic agents. In this study, we explore the interactions of betulinic acid (BA), oleanolic acid (OA), ursolic acid (UA), and maslinic acid (MA) against FadA5. Studies have identified FadA5, a trifunctional enzyme-like thiolase, as a target towards Mycobacterium tuberculosis inhibition. The investigation involves molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) applications. Analyses of the four pentacyclic triterpenoids binding to FadA5 showed appreciable bioactivity against FadA5. The application of two or more theoretical models to unravel ligand-enzyme binding energies can pave the way for accurate binding affinity prediction and validation.
The involvement of cellular oxidative stress in antibacterial therapy has remained a topical issu... more The involvement of cellular oxidative stress in antibacterial therapy has remained a topical issue over the years. In this study, the contribution of oxidative stress to astaxanthin-mediated bacterial lethality was evaluated in silico and in vitro. For the in vitro analysis, the minimum inhibitory concentration (MIC) of astaxanthin was lower than that of novobiocin against Staphylococcus aureus but generally higher than those of the reference antibiotics against other test organisms. The level of superoxide anion of the tested organisms increased significantly following treatment with astaxanthin when compared with DMSO-treated cells. This increase compared favorably with those observed with the reference antibiotics and was consistent with a decrease in the concentration of glutathione (GSH) and corresponding significant increase in ADP/ATP ratio. These observations are suggestive of probable involvement of oxidative stress in antibacterial capability of astaxanthin and in agreemen...
1. Department of Chemistry, Faculty of Science, Yobe State University, PMB 1144 Damaturu, Nigeria... more 1. Department of Chemistry, Faculty of Science, Yobe State University, PMB 1144 Damaturu, Nigeria 2. Department of Chemistry, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, Republic of South Africa. [E-mail: chemibrabal@gmail.com, Tel: +234(0)8035879874] 3. Department of Chemistry, Faculty of Sciences, University of Jos, Jos, Nigeria. 4. Department of Biochemistry and Microbiology, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, Republic of South Africa.
The use of herbs (medicinal plants) for the treatment of diseases is as old as the history of man... more The use of herbs (medicinal plants) for the treatment of diseases is as old as the history of mankind. Sterculia setigera is an example of such plant endowed in nature to serve the needs of man. Folkloric claims on antibacterial activity of S. setigera were investigated in-vitro on a micro-scale using the Alamar Blue Assay. Three of four successive solvent extractions of the plant leaves extracts inhibited the growth of a virulent strain of Mycobacterium tuberculosis, H37Rv (ATCC27294) in the concentrations tested (1-128 µg/ml). The minimum inhibitory concentration (MIC) determined for the hexane, dichloromethane and ethyl acetate extracts were 84 µg/ml, 62 µg/ml and 128 µg/ml respectively. The combined active extracts were subjected to an extensive bioactivity-guided fractionation using a combination of normal phase (NP VLC) and reverse phase (RP MPLC) chromatography. Purification of active fractions led to pure sub-fractions with good activity (MICs 15.13 µg/ml-31.43 µg/ml). The c...
The isolation of pure ursolic acid (UA) from most plants presents a problem because it often come... more The isolation of pure ursolic acid (UA) from most plants presents a problem because it often comes as a mixture with its isomer, oleanolic acid (OA). In this study the separation of UA from OA/UA mixture obtained from Mimusops caffra was achieved through acetylation to give the acetate of UA and OA respectively. Pure UA (90%) was then obtained by simple de-acetylation of the UA acetate. The resulting UA was used as template for the semi-synthesis of three triterpenoids derivatives. This study confirmed the various reports in literature that UA is always accompanied by its isomer oleanolic acid (OA). This article further reports for the first time the synthesis of 3-acetyl-UA-28-cinnamate. The cytotoxicity of all compounds was evaluated on human embryonic cells (HEK293) and human hepatocellular carcinoma cells (HepG2) by MTT assay. All the compounds studied exhibited low toxicity levels with IC50 > 300 µg/ml.
Ancient people used medicinal plant extract as ingredients in tradomedical portions and poisons. ... more Ancient people used medicinal plant extract as ingredients in tradomedical portions and poisons. Over time, these traditional treatments have had the chance to become refined based on efficacy and safety. It was therefore hypothesised that plants that were used in the past and are still used today to treat symptoms associated with a particular disease condition are more likely to contain pharmacologically active metabolites than plants that have not been used continuously. The use of E. grandis in traditional medicines has been document. Ursolic acid (3β- hydroxyurs-12-en-28-oic acid) was isolated from the leaves of Eucarlyptus grandis. Column chromatography (normal phase), IR, LC-MS and NMR techniques were employed for the isolation and characterization of the compound. Presence of ursolic acid, a pentacyclic triterpene carboxylic acid in the leaves of E. grandis gives credence to the ethnomedical use of the plant leaves in the treatment of diseases.
1. Department. of Chemistry, Faculty of Science, Yobe State University, PMB 1144 Damaturu, Nigeri... more 1. Department. of Chemistry, Faculty of Science, Yobe State University, PMB 1144 Damaturu, Nigeria [E-mail: chemibrabal@gmail.com; Tel: +234(0)8035879874] 2. Department of Chemistry, Faculty of Sciences and Agriculture, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, Republic of South Africa and Research, Innovation & Development Director of Life-Promoters Biosciences (Pty) Ltd, 5 Ferrara Gardens, Westville North 3629, South Africa.
Platelet dysfunctions are implicated in cardiovascular diseases. Management of abnormal platelet ... more Platelet dysfunctions are implicated in cardiovascular diseases. Management of abnormal platelet aggregations with natural products is a promising approach to the treatment of cardiovascular diseases. In this study, betulinic acid (BA) isolated from Melaleuca bracteata leaf extract, and its acetyl derivative (3-β acetylbetulinic acid) (BAA) were investigated for their antiplatelet aggregation and cytotoxic activity. Structures of the compounds were established and confirmed through spectral (nuclear magnetic resonance [NMR], infrared [IR], mass spectroscopy [MS]) data analysis. The antiplatelet aggregation activity of the compounds was separately evaluated on collagen, adenosine diphosphate [ADP], thrombin and epinephrine induced rat platelet aggregations. The 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay was used to determine the cytotoxic effect of the compounds against human embryonic kidney (HEK293) and hepatocellular carcinoma (HEPG2) c...
Diabetes mellitus (DM) is a chronic metabolic disorder which has become a major risk to the healt... more Diabetes mellitus (DM) is a chronic metabolic disorder which has become a major risk to the health of humankind, as its global prevalence is increasing rapidly. Currently available treatment options in modern medicine have several adverse effects. Thus, there is an urgent need to develop alternative cost-effective, safe, and active treatments for diabetes. In this regard, medicinal plants provide the best option for new therapeutic remedies desired to be effective and safe. Recently, we focused our attention on drimane sesquiterpenes as potential sources of antimalarial and antidiabetic agents. In this study, iso-mukaadial acetate (Iso) (1), a drimane-type sesquiterpenoid from the ground stem bark of Warburgia salutaris, was investigated for glucose uptake enhancement in the L6 rat myoblast cell line. In vitro assays with L6 skeletal muscle cells were used to test for cytotoxicity, glucose utilisation, and western blot analysis. Additionally, the inhibition of carbohydrate digestive...
Oleanolic acid is a triterpenoid that has shown in vitro cytotoxic activity against human tumour ... more Oleanolic acid is a triterpenoid that has shown in vitro cytotoxic activity against human tumour cells and is known to be present in many higher plants. Oleanolic acid is known to have some biological potential including anticancer property. Oleanolic acid was isolated from the ethyl acetate fraction of Syzygium aromaticum seed with an aim of dervitatising the functional group and evaluating the biological activities of the semi-synthesised compounds. Acylation of the alcohol functional group of the oleanolic acid afforded the opportunity of hydrazine reaction to give 3-acetoleanolic hydrazide. Further reaction of 3-acetoleanolic hydrazide with benzyladehyde, glacial acetic acid and methanol resulted in the synthesis of the corresponding 3-acetoxyoleanolic hydrazone. The semi-synthetic oleanolic acid derivatives did not exhibit enhanced cytotoxic activity over oleanolic acid itself. 3-acetoxyoleanolic hydrazide has a potent anticancer activity.
Acquired immunodeficiency syndrome (AIDS), one of the deadliest global diseases, is caused by the... more Acquired immunodeficiency syndrome (AIDS), one of the deadliest global diseases, is caused by the Human Immunodeficiency Virus (HIV). To date, there are no known conventional drugs that can cure HIV/AIDS, and this has prompted continuous scientific efforts in the search for novel and potent anti-HIV therapies. In this study, molecular dynamics simulation (MDS) and computational techniques were employed to investigate the inhibitory potential of bioactive compounds from selected South African indigenous plants against HIV-1 subtype C protease (HIVpro). Of the eight compounds (CMG, MA, UA, CA, BA, UAA, OAA and OA) evaluated, only six (CMG (−9.9 kcal/mol), MA (−9.3 kcal/mol), CA (−9.0 kcal/mol), BA (−8.3 kcal/mol), UAA (−8.5 kcal/mol), and OA (−8.6 kcal/mol)) showed favourable activities against HIVpro and binding landscapes like the reference FDA-approved drugs, Lopinavir (LPV) and Darunavir (DRV), with CMG and MA having the highest binding affinities. Using the structural analysis (r...
African Journal of Microbiology Research, Nov 16, 2011
ABSTRACT Phytochemical investigation of Eucalyptus grandis, a plant with many industrial and trad... more ABSTRACT Phytochemical investigation of Eucalyptus grandis, a plant with many industrial and traditional applications, led to the isolation of 3β-hydroxyurs-2-en-28-oic acid (FJ-2) and the synthesis of 3β-acetylurs-12-en-28-oic acid (FJ-6), with antiplatelet aggregation activity. Platelet aggregation was induced by thrombin a platelet protease-activated receptors subtype I and IV, adenosine diphosphate (ADP) a potent agonist to platelet G protein-coupled P2Y receptor and epinephrine. The results showed FJ-2 had the highest percentage inhibition (87.8 ± 1.81) which was observed to be significantly (P < 0.05) higher than the standards heparin (65.9 ± 0.91) and aspirin (65.4 ± 0.8) at a concentration of 1.0 mg/ml, using thrombin-as agonist. But this percentage inhibition was observed to decrease with increase in the concentration of FJ-2; this implied an optimal concentration (≤ 1.0 mg/ml) for inhibition of platelet aggregation by FJ-2, above which inhibition decreases. FJ-6 showed a dose dependent increase in percentage inhibition (51.4 ± 0.65 at 1.0 mg/ml and 73.8 ± 1.72 at 10 mg/ml). The two compounds differ only in their functionality but behave differently towards platelet aggregation inhibition. This preliminary result suggests that FJ-2 and FJ-6 may be taken as candidate lead natural compounds to be considered in the search for natural products with beneficial effects on aberrant platelet activation mediated cardiovascular disorders.
Leptospermum petersonii (family Myrtaceae) is often cultivated for ornamental purposes but also s... more Leptospermum petersonii (family Myrtaceae) is often cultivated for ornamental purposes but also serves as a rich source of bioactive essential oils. While several studies focused on the activities of the essential oils, this study analysed the potential of spent L. petersonii leaves as a natural food preservative. Method: We investigated the in vitro antioxidant and antimicrobial activities of crude L. petersonii extracts against activities of the purified isolated flavonoid, 6-methyltectochrysin, which was characterized using spectroscopic methods. The antioxidant assays followed ORAC, FRAP and TEAC tests. The antimicrobial activities of the extract and purified flavonoid were analysed against six multi-drug resistant microbial strains in broth dilution assays. Result: The results revealed that both the crude extracts and isolated 6-methyltectochrysin exhibited positive radical ion scavenging antioxidant potential, however the crude extract was about 6-fold more potent antioxidant ...
A group of bioactive compounds known as triterpenoids, which are often found in plant materials, ... more A group of bioactive compounds known as triterpenoids, which are often found in plant materials, have been tested to possess nutritional and pharmaceutical activity. These plant components are referred to as nutraceuticals, and are used as therapeutic agents. In this study, we explore the interactions of betulinic acid (BA), oleanolic acid (OA), ursolic acid (UA), and maslinic acid (MA) against FadA5. Studies have identified FadA5, a trifunctional enzyme-like thiolase, as a target towards Mycobacterium tuberculosis inhibition. The investigation involves molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) applications. Analyses of the four pentacyclic triterpenoids binding to FadA5 showed appreciable bioactivity against FadA5. The application of two or more theoretical models to unravel ligand-enzyme binding energies can pave the way for accurate binding affinity prediction and validation.
The involvement of cellular oxidative stress in antibacterial therapy has remained a topical issu... more The involvement of cellular oxidative stress in antibacterial therapy has remained a topical issue over the years. In this study, the contribution of oxidative stress to astaxanthin-mediated bacterial lethality was evaluated in silico and in vitro. For the in vitro analysis, the minimum inhibitory concentration (MIC) of astaxanthin was lower than that of novobiocin against Staphylococcus aureus but generally higher than those of the reference antibiotics against other test organisms. The level of superoxide anion of the tested organisms increased significantly following treatment with astaxanthin when compared with DMSO-treated cells. This increase compared favorably with those observed with the reference antibiotics and was consistent with a decrease in the concentration of glutathione (GSH) and corresponding significant increase in ADP/ATP ratio. These observations are suggestive of probable involvement of oxidative stress in antibacterial capability of astaxanthin and in agreemen...
1. Department of Chemistry, Faculty of Science, Yobe State University, PMB 1144 Damaturu, Nigeria... more 1. Department of Chemistry, Faculty of Science, Yobe State University, PMB 1144 Damaturu, Nigeria 2. Department of Chemistry, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, Republic of South Africa. [E-mail: chemibrabal@gmail.com, Tel: +234(0)8035879874] 3. Department of Chemistry, Faculty of Sciences, University of Jos, Jos, Nigeria. 4. Department of Biochemistry and Microbiology, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, Republic of South Africa.
The use of herbs (medicinal plants) for the treatment of diseases is as old as the history of man... more The use of herbs (medicinal plants) for the treatment of diseases is as old as the history of mankind. Sterculia setigera is an example of such plant endowed in nature to serve the needs of man. Folkloric claims on antibacterial activity of S. setigera were investigated in-vitro on a micro-scale using the Alamar Blue Assay. Three of four successive solvent extractions of the plant leaves extracts inhibited the growth of a virulent strain of Mycobacterium tuberculosis, H37Rv (ATCC27294) in the concentrations tested (1-128 µg/ml). The minimum inhibitory concentration (MIC) determined for the hexane, dichloromethane and ethyl acetate extracts were 84 µg/ml, 62 µg/ml and 128 µg/ml respectively. The combined active extracts were subjected to an extensive bioactivity-guided fractionation using a combination of normal phase (NP VLC) and reverse phase (RP MPLC) chromatography. Purification of active fractions led to pure sub-fractions with good activity (MICs 15.13 µg/ml-31.43 µg/ml). The c...
The isolation of pure ursolic acid (UA) from most plants presents a problem because it often come... more The isolation of pure ursolic acid (UA) from most plants presents a problem because it often comes as a mixture with its isomer, oleanolic acid (OA). In this study the separation of UA from OA/UA mixture obtained from Mimusops caffra was achieved through acetylation to give the acetate of UA and OA respectively. Pure UA (90%) was then obtained by simple de-acetylation of the UA acetate. The resulting UA was used as template for the semi-synthesis of three triterpenoids derivatives. This study confirmed the various reports in literature that UA is always accompanied by its isomer oleanolic acid (OA). This article further reports for the first time the synthesis of 3-acetyl-UA-28-cinnamate. The cytotoxicity of all compounds was evaluated on human embryonic cells (HEK293) and human hepatocellular carcinoma cells (HepG2) by MTT assay. All the compounds studied exhibited low toxicity levels with IC50 > 300 µg/ml.
Ancient people used medicinal plant extract as ingredients in tradomedical portions and poisons. ... more Ancient people used medicinal plant extract as ingredients in tradomedical portions and poisons. Over time, these traditional treatments have had the chance to become refined based on efficacy and safety. It was therefore hypothesised that plants that were used in the past and are still used today to treat symptoms associated with a particular disease condition are more likely to contain pharmacologically active metabolites than plants that have not been used continuously. The use of E. grandis in traditional medicines has been document. Ursolic acid (3β- hydroxyurs-12-en-28-oic acid) was isolated from the leaves of Eucarlyptus grandis. Column chromatography (normal phase), IR, LC-MS and NMR techniques were employed for the isolation and characterization of the compound. Presence of ursolic acid, a pentacyclic triterpene carboxylic acid in the leaves of E. grandis gives credence to the ethnomedical use of the plant leaves in the treatment of diseases.
1. Department. of Chemistry, Faculty of Science, Yobe State University, PMB 1144 Damaturu, Nigeri... more 1. Department. of Chemistry, Faculty of Science, Yobe State University, PMB 1144 Damaturu, Nigeria [E-mail: chemibrabal@gmail.com; Tel: +234(0)8035879874] 2. Department of Chemistry, Faculty of Sciences and Agriculture, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, Republic of South Africa and Research, Innovation & Development Director of Life-Promoters Biosciences (Pty) Ltd, 5 Ferrara Gardens, Westville North 3629, South Africa.
Platelet dysfunctions are implicated in cardiovascular diseases. Management of abnormal platelet ... more Platelet dysfunctions are implicated in cardiovascular diseases. Management of abnormal platelet aggregations with natural products is a promising approach to the treatment of cardiovascular diseases. In this study, betulinic acid (BA) isolated from Melaleuca bracteata leaf extract, and its acetyl derivative (3-β acetylbetulinic acid) (BAA) were investigated for their antiplatelet aggregation and cytotoxic activity. Structures of the compounds were established and confirmed through spectral (nuclear magnetic resonance [NMR], infrared [IR], mass spectroscopy [MS]) data analysis. The antiplatelet aggregation activity of the compounds was separately evaluated on collagen, adenosine diphosphate [ADP], thrombin and epinephrine induced rat platelet aggregations. The 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay was used to determine the cytotoxic effect of the compounds against human embryonic kidney (HEK293) and hepatocellular carcinoma (HEPG2) c...
Diabetes mellitus (DM) is a chronic metabolic disorder which has become a major risk to the healt... more Diabetes mellitus (DM) is a chronic metabolic disorder which has become a major risk to the health of humankind, as its global prevalence is increasing rapidly. Currently available treatment options in modern medicine have several adverse effects. Thus, there is an urgent need to develop alternative cost-effective, safe, and active treatments for diabetes. In this regard, medicinal plants provide the best option for new therapeutic remedies desired to be effective and safe. Recently, we focused our attention on drimane sesquiterpenes as potential sources of antimalarial and antidiabetic agents. In this study, iso-mukaadial acetate (Iso) (1), a drimane-type sesquiterpenoid from the ground stem bark of Warburgia salutaris, was investigated for glucose uptake enhancement in the L6 rat myoblast cell line. In vitro assays with L6 skeletal muscle cells were used to test for cytotoxicity, glucose utilisation, and western blot analysis. Additionally, the inhibition of carbohydrate digestive...
Oleanolic acid is a triterpenoid that has shown in vitro cytotoxic activity against human tumour ... more Oleanolic acid is a triterpenoid that has shown in vitro cytotoxic activity against human tumour cells and is known to be present in many higher plants. Oleanolic acid is known to have some biological potential including anticancer property. Oleanolic acid was isolated from the ethyl acetate fraction of Syzygium aromaticum seed with an aim of dervitatising the functional group and evaluating the biological activities of the semi-synthesised compounds. Acylation of the alcohol functional group of the oleanolic acid afforded the opportunity of hydrazine reaction to give 3-acetoleanolic hydrazide. Further reaction of 3-acetoleanolic hydrazide with benzyladehyde, glacial acetic acid and methanol resulted in the synthesis of the corresponding 3-acetoxyoleanolic hydrazone. The semi-synthetic oleanolic acid derivatives did not exhibit enhanced cytotoxic activity over oleanolic acid itself. 3-acetoxyoleanolic hydrazide has a potent anticancer activity.
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