Ptycholobium is a genus related to Tephrosia which comprises only three species. Compared to Teph... more Ptycholobium is a genus related to Tephrosia which comprises only three species. Compared to Tephrosia, which has been phytochemically and pharmacologically studied, Ptycholobium species have only few or no reports on their chemical constituents. Moreover, no studies on the cytotoxic activities of its secondary metabolites have been previously documented. From the non polar fractions of the roots bark of Ptycholobium contortum (syn Tephrosia contorta), two new pterocarpans: seputhecarpan C 1 and seputhecarpan D 2 and a new pyrone derivative, ptycholopyrone A 3 were isolated. Alongside, five known compounds identified as 3-α,α-dimethylallyl-4-methoxy-6-styryl-α-pyrone or mundulea lactone 4, glyasperin F 5, seputhecarpan A 6, seputheisoflavone 7 and 5-O-methyl-myo-inositol or sequoyitol 8 were also obtained. Their structures were established by the mean means of spectroscopic data in conjunction to those reported in literature. The NMR assignment of the major compound mundulea lactone...
Human Immunodeficiency Virus (HIV) strains resistant to licensed anti-retroviral drugs (ARVs) con... more Human Immunodeficiency Virus (HIV) strains resistant to licensed anti-retroviral drugs (ARVs) continue to emerge. On the African continent, uneven access to ARVs combined with occurrence of side-effects after prolonged ARV therapy have led to searches for traditional medicines as alternative or complementary remedies to conventional HIV/AIDS management. Here we characterize a specific three-step traditional HIV/AIDS treatment regimen consisting of Cassia sieberiana root, Vitex doniana root, and Croton megalobotrys bark by combining qualitative interviews of traditional medical knowledge users in Botswana with in vitro HIV replication studies. Crude extracts from a total of seven medicinal plants were tested for in vitro cytotoxicity and inhibition of wild-type (NL4.3) and ARV-resistant HIV-1 replication in an immortalized GFP-reporter CD4+ T-cell line. C. sieberiana root, V. doniana root, and C. megalobotrys bark extracts inhibited HIV-1NL4.3 replication with dose-dependence and without concomitant cytotoxicity. C. sieberiana and V. doniana extracts inhibited HIV-1 replication by 50% at 84.8 µg/mL and at 25 µg/mL, respectively, while C. megalobotrys extracts inhibited HIV-1 replication by a maximum of 45% at concentrations as low as 0.05 µg/mL. Extracts did not interfere with antiviral activities of licensed ARVs when applied in combination and exhibited comparable efficacies against viruses harboring major resistance mutations to licensed protease, reverse-transcriptase, or integrase inhibitors. We report for the first time a three-step traditional HIV/AIDS regimen, used alone or in combination with standard ARV regimens, where each step exhibited more potent ability to inhibit HIV replication in vitro. Our observations support the "reverse pharmacology" model where documented clinical experiences are used to identify natural products of therapeutic value.
Purpose: The purpose of this paper is to understand the perceptions and attitudes of community me... more Purpose: The purpose of this paper is to understand the perceptions and attitudes of community members towards traditional medicines, including their safety, authenticity and efficacy. Methodology: A participatory exploratory study design was chosen, combined with a multiple approach to data collection and analysis using consultative and report-back workshops, individual interviews and focus-group discussions. Findings: Eighty-four per cent of the community members felt that traditional medicines are safe, especially if prescribed instructions are followed. Some of the interviewees felt that traditional healers were better equipped to treat certain diseases whilst biomedical doctors were more efficient in others, hence complementary. The efficacy of traditional medicines was undoubted; however , the authenticity of some traditional healers was questioned.
ABSTRACT Seven homoisoflavonoids and one stilbenoid, 3-(4′-methoxybenzyl)-6,7-dihydroxy-5-methoxy... more ABSTRACT Seven homoisoflavonoids and one stilbenoid, 3-(4′-methoxybenzyl)-6,7-dihydroxy-5-methoxychroman-4-one (1) which is new; 3-(4′-methoxybenzyl)-6-hydroxy-5,7-dimethoxychroman-4-one (2); 3-(4′-methoxybenzyl)-5,7-dimethoxychroman-4-one (3); 3-(3′-hydroxy-4′-methoxybenzyl)-5,7-dimethoxychroman-4-one (4); 3-(4′-methoxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one (5); 3-(4′-hydroxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one (6); 3-(4′-hydroxybenzylidene)-5,7-dihydroxychroman-4-one (7) and 4,3′,5′-trihydroxy-3-methoxystilbene (8), were isolated from the yellow inter-bulb deposits from Scilla nervosa. The structures of these compounds were elucidated by 1D- and 2D-NMR and mass spectrometry. A number of extracts, fractions and compounds tested displayed bacterostatic activity with MICs ranging between 0.156 and 1.250 mg/ml. Two extracts displayed significant α-glucosidase inhibitory activity and a number of extracts, fractions and compounds showed strong antioxidant activity with, compounds 1, 2 and 8 displaying lower MECs than the positive control ascorbic acid (0.0156 mg/ml).
Polyphenols are a versatile class of compounds that represent secondary metabolites from higher p... more Polyphenols are a versatile class of compounds that represent secondary metabolites from higher plants and which are abundantly present in the human diet. Epidemiological data suggest protective effects of polyhenols in relation to cancer, cardiovascular diseases, diabetes, infectious diseases and age-related conditions. HIV/AIDS remains prevalent in many parts of the world as acute infection and as anti-retroviral drug (ARV)-managed chronic disease. Due to the nature of the human immune deficiency virus (HIV) and an increased use of ARVs many drug-resistant HIV strains have emerged and continue to do so. This makes it impossible to rely on one standard drug treatment regime. This review summarizes anti- HIV activities of polyphenols. It highlights the diversity of modes of action by which polyphenols - according to their respective compound classes - exert their activities. Additionally, this review discusses polyphenols as multi-target anti-HIV agents and provides the context of in-vivo and clinical data. Based on the presented data, a three-pronged approach for further anti-HIV drug discovery is suggested applying methods of combinatorial medicinal chemistry on the diverse and sometimes unique scaffolds of polyphenols. The latter being selected according to the approach of 'reverse pharmacology' as a creative way to place safety and other clinical consideration at the beginning of the drug discovery- and development process.
The determination of four potentially toxic heavy metals, arsenic, chromium, lead and nickel in t... more The determination of four potentially toxic heavy metals, arsenic, chromium, lead and nickel in twelve plant species used for the treatment of perceived HIV and AIDS-associated opportunistic infections by traditional healers in Ngamiland District in Northern Botswana, a metal mining area, was carried out using atomic absorption spectrometry. The medicinal plants; Dichrostachys cinerea, Maerua angolensis, Mimusops zeyheri, Albizia anthelmintica, Plumbago zeylanica, Combretum imberbe, Indigofera flavicans, Clerodendrum ternatum, Solanum panduriforme, Capparis tomentosa, Terminalia sericea and Maytenus senegalensis contained heavy metals in varying quantities: arsenic 0.19-0.54 μg g(-1), chromium 0.15-1.27 μg g(-1), lead 0.12-0.23 μg g(-1) and nickel 0.09-0.21 μg g(-1) of dry weight. Chromium was found to be the most abundant followed by arsenic and lead. Nickel was undetectable in nine plant species. M. senegalensis contained the largest amounts of arsenic, chromium and lead. All meta...
The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, comb... more The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integ...
The total synthesis of a potent antiplasmodial natural bichalcone, rhuschalcone VI, is described ... more The total synthesis of a potent antiplasmodial natural bichalcone, rhuschalcone VI, is described starting from simple and available resorcinol and 4-hydroxybenzaldehyde. Key steps include the solvent-free Aldol syntheses of chalcones, and the successful application of the Suzuki-Miyaura coupling reaction in the synthesis of bichalcones. The present work constitutes a general method for the rapid syntheses of a number of bichalcones related to rhuschalcone VI. Some of the bichalcones showed moderate antiprotozoal activities against Bodo caudatus, a preliminary screening system for antitrypanosomal activities, most of them with little or no cytotoxicity.
Ptycholobium is a genus related to Tephrosia which comprises only three species. Compared to Teph... more Ptycholobium is a genus related to Tephrosia which comprises only three species. Compared to Tephrosia, which has been phytochemically and pharmacologically studied, Ptycholobium species have only few or no reports on their chemical constituents. Moreover, no studies on the cytotoxic activities of its secondary metabolites have been previously documented. From the non polar fractions of the roots bark of Ptycholobium contortum (syn Tephrosia contorta), two new pterocarpans: seputhecarpan C 1 and seputhecarpan D 2 and a new pyrone derivative, ptycholopyrone A 3 were isolated. Alongside, five known compounds identified as 3-α,α-dimethylallyl-4-methoxy-6-styryl-α-pyrone or mundulea lactone 4, glyasperin F 5, seputhecarpan A 6, seputheisoflavone 7 and 5-O-methyl-myo-inositol or sequoyitol 8 were also obtained. Their structures were established by the mean means of spectroscopic data in conjunction to those reported in literature. The NMR assignment of the major compound mundulea lactone...
Human Immunodeficiency Virus (HIV) strains resistant to licensed anti-retroviral drugs (ARVs) con... more Human Immunodeficiency Virus (HIV) strains resistant to licensed anti-retroviral drugs (ARVs) continue to emerge. On the African continent, uneven access to ARVs combined with occurrence of side-effects after prolonged ARV therapy have led to searches for traditional medicines as alternative or complementary remedies to conventional HIV/AIDS management. Here we characterize a specific three-step traditional HIV/AIDS treatment regimen consisting of Cassia sieberiana root, Vitex doniana root, and Croton megalobotrys bark by combining qualitative interviews of traditional medical knowledge users in Botswana with in vitro HIV replication studies. Crude extracts from a total of seven medicinal plants were tested for in vitro cytotoxicity and inhibition of wild-type (NL4.3) and ARV-resistant HIV-1 replication in an immortalized GFP-reporter CD4+ T-cell line. C. sieberiana root, V. doniana root, and C. megalobotrys bark extracts inhibited HIV-1NL4.3 replication with dose-dependence and without concomitant cytotoxicity. C. sieberiana and V. doniana extracts inhibited HIV-1 replication by 50% at 84.8 µg/mL and at 25 µg/mL, respectively, while C. megalobotrys extracts inhibited HIV-1 replication by a maximum of 45% at concentrations as low as 0.05 µg/mL. Extracts did not interfere with antiviral activities of licensed ARVs when applied in combination and exhibited comparable efficacies against viruses harboring major resistance mutations to licensed protease, reverse-transcriptase, or integrase inhibitors. We report for the first time a three-step traditional HIV/AIDS regimen, used alone or in combination with standard ARV regimens, where each step exhibited more potent ability to inhibit HIV replication in vitro. Our observations support the "reverse pharmacology" model where documented clinical experiences are used to identify natural products of therapeutic value.
Purpose: The purpose of this paper is to understand the perceptions and attitudes of community me... more Purpose: The purpose of this paper is to understand the perceptions and attitudes of community members towards traditional medicines, including their safety, authenticity and efficacy. Methodology: A participatory exploratory study design was chosen, combined with a multiple approach to data collection and analysis using consultative and report-back workshops, individual interviews and focus-group discussions. Findings: Eighty-four per cent of the community members felt that traditional medicines are safe, especially if prescribed instructions are followed. Some of the interviewees felt that traditional healers were better equipped to treat certain diseases whilst biomedical doctors were more efficient in others, hence complementary. The efficacy of traditional medicines was undoubted; however , the authenticity of some traditional healers was questioned.
ABSTRACT Seven homoisoflavonoids and one stilbenoid, 3-(4′-methoxybenzyl)-6,7-dihydroxy-5-methoxy... more ABSTRACT Seven homoisoflavonoids and one stilbenoid, 3-(4′-methoxybenzyl)-6,7-dihydroxy-5-methoxychroman-4-one (1) which is new; 3-(4′-methoxybenzyl)-6-hydroxy-5,7-dimethoxychroman-4-one (2); 3-(4′-methoxybenzyl)-5,7-dimethoxychroman-4-one (3); 3-(3′-hydroxy-4′-methoxybenzyl)-5,7-dimethoxychroman-4-one (4); 3-(4′-methoxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one (5); 3-(4′-hydroxybenzylidene)-5,7-dihydroxy-6-methoxychroman-4-one (6); 3-(4′-hydroxybenzylidene)-5,7-dihydroxychroman-4-one (7) and 4,3′,5′-trihydroxy-3-methoxystilbene (8), were isolated from the yellow inter-bulb deposits from Scilla nervosa. The structures of these compounds were elucidated by 1D- and 2D-NMR and mass spectrometry. A number of extracts, fractions and compounds tested displayed bacterostatic activity with MICs ranging between 0.156 and 1.250 mg/ml. Two extracts displayed significant α-glucosidase inhibitory activity and a number of extracts, fractions and compounds showed strong antioxidant activity with, compounds 1, 2 and 8 displaying lower MECs than the positive control ascorbic acid (0.0156 mg/ml).
Polyphenols are a versatile class of compounds that represent secondary metabolites from higher p... more Polyphenols are a versatile class of compounds that represent secondary metabolites from higher plants and which are abundantly present in the human diet. Epidemiological data suggest protective effects of polyhenols in relation to cancer, cardiovascular diseases, diabetes, infectious diseases and age-related conditions. HIV/AIDS remains prevalent in many parts of the world as acute infection and as anti-retroviral drug (ARV)-managed chronic disease. Due to the nature of the human immune deficiency virus (HIV) and an increased use of ARVs many drug-resistant HIV strains have emerged and continue to do so. This makes it impossible to rely on one standard drug treatment regime. This review summarizes anti- HIV activities of polyphenols. It highlights the diversity of modes of action by which polyphenols - according to their respective compound classes - exert their activities. Additionally, this review discusses polyphenols as multi-target anti-HIV agents and provides the context of in-vivo and clinical data. Based on the presented data, a three-pronged approach for further anti-HIV drug discovery is suggested applying methods of combinatorial medicinal chemistry on the diverse and sometimes unique scaffolds of polyphenols. The latter being selected according to the approach of 'reverse pharmacology' as a creative way to place safety and other clinical consideration at the beginning of the drug discovery- and development process.
The determination of four potentially toxic heavy metals, arsenic, chromium, lead and nickel in t... more The determination of four potentially toxic heavy metals, arsenic, chromium, lead and nickel in twelve plant species used for the treatment of perceived HIV and AIDS-associated opportunistic infections by traditional healers in Ngamiland District in Northern Botswana, a metal mining area, was carried out using atomic absorption spectrometry. The medicinal plants; Dichrostachys cinerea, Maerua angolensis, Mimusops zeyheri, Albizia anthelmintica, Plumbago zeylanica, Combretum imberbe, Indigofera flavicans, Clerodendrum ternatum, Solanum panduriforme, Capparis tomentosa, Terminalia sericea and Maytenus senegalensis contained heavy metals in varying quantities: arsenic 0.19-0.54 μg g(-1), chromium 0.15-1.27 μg g(-1), lead 0.12-0.23 μg g(-1) and nickel 0.09-0.21 μg g(-1) of dry weight. Chromium was found to be the most abundant followed by arsenic and lead. Nickel was undetectable in nine plant species. M. senegalensis contained the largest amounts of arsenic, chromium and lead. All meta...
The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, comb... more The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integ...
The total synthesis of a potent antiplasmodial natural bichalcone, rhuschalcone VI, is described ... more The total synthesis of a potent antiplasmodial natural bichalcone, rhuschalcone VI, is described starting from simple and available resorcinol and 4-hydroxybenzaldehyde. Key steps include the solvent-free Aldol syntheses of chalcones, and the successful application of the Suzuki-Miyaura coupling reaction in the synthesis of bichalcones. The present work constitutes a general method for the rapid syntheses of a number of bichalcones related to rhuschalcone VI. Some of the bichalcones showed moderate antiprotozoal activities against Bodo caudatus, a preliminary screening system for antitrypanosomal activities, most of them with little or no cytotoxicity.
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