Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potenti... more Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propo...
Neglected tropical diseases are major health hazards in developing countries. Annually, up to 30 ... more Neglected tropical diseases are major health hazards in developing countries. Annually, up to 30 million people are affected by either Chagas disease, African trypansomiasis or leishmaniasis, and more than 200 million by malaria. Most of the currently available drugs have drawbacks in terms of toxicity, limited oral availability, development of resistance, or non-affordability. Tropical plants of the arid zones are a treasure chest for the discovery of bioactive secondary metabolites. This study aims to compile Sudanese medicinal plants, validate their antiprotozoal activities, and identify active molecules. We have performed a survey of medicinal plants of Sudan and selected 62 that are being used in Sudanese traditional medicine. From these, we collected materials such as leaves, stem, bark, or fruit. The plant materials were extracted in 70% ethanol and further fractionated by liquid-liquid partitioning using solvents of increasing polarity. This resulted in a library of 235 fractions. The library was tested in vitro against Plasmodium falciparum (erythrocytic stages), Trypanosoma brucei rhodesiense (bloodstream forms), Trypanosoma cruzi (intracellular amastigotes), and Leishmania donovani (axenic amastigotes). Active fractions were also tested for cytotoxicity. Of the 235 fractions, 125 showed growth inhibitory activity >80% at 10 mg/ml, and >50% at 2 mg/ml against at least one of the protozoan parasites. Plasmodium falciparum was the most sensitive of the parasites, followed by T. b. rhodesiense and L. donovani. Only few hits were identified for T. cruzi, and these were not selective. Contrary to expectation based on phylogeny, but in agreement with previous results, a large number of extracts displayed mutual activity against T. brucei and P. falciparum. HPLC-based activity profiling for selected active extracts was performed to identify the bioactive principles. Active compounds identified by dereplication were guieranone A from Guiera senegalensis J.F.Gmel.; pseudosemiglabrin from Tephrosia apollinea (Delile) DC; ellagic acid and quercetin from Terminalia leiocarpa (DC.) Baill.; and catechin, ethyl gallate, and epicatechin gallate from Vachellia nilotica (L.) P.J.H.Hurter & Mabb. Also the extracts of Croton gratissimus var. gratissimus and Cuscuta hyalina Roth ex Schult. exhibited promising antitrypanosomatid activity. This assessment provides a comprehensive overview of Sudanese medicinal plants and supports the notion that they are a potential source of bioactive molecules against protozoan parasites.
The uses of 40 species of the most commonly prescribed medicinal plants in the Dongola Province, ... more The uses of 40 species of the most commonly prescribed medicinal plants in the Dongola Province, Northern Sudan are described.
We present an in vitro susceptibility assay for Madurella mycetomatis hyphae using resazurin for ... more We present an in vitro susceptibility assay for Madurella mycetomatis hyphae using resazurin for endpoint reading. Using this assay, reproducible MICs were obtained for amphotericin B, itraconazole, voriconazole, posaconazole, terbinafine, and micafungin.
A screening of Sudanese medicinal plants for antiprotozoal activities revealed that the chlorofor... more A screening of Sudanese medicinal plants for antiprotozoal activities revealed that the chloroform and water fractions of the ethanolic root extract of Haplophyllum tuberculatum exhibited appreciable bioactivity against Leishmania donovani. The antileishmanial activity was tracked by HPLC-based activity profiling, and eight compounds were isolated from the chloroform fraction. These included lignans tetrahydrofuroguaiacin B (1), nectandrin B (2), furoguaiaoxidin (7), and 3,3′-dimethoxy-4,4′-dihydroxylignan-9-ol (10), and four cinnamoylphenethyl amides, namely dihydro-feruloyltyramine (5), (E)-N-feruloyltyramine (6), N,N′-diferuloylputrescine (8), and 7′-ethoxy-feruloyltyramine (9). The water fraction yielded steroid saponins 11–13. Compounds 1, 2, and 5–13 are reported for the first time from Haplophyllum species and the family Rutaceae. The antiprotozoal activity of the compounds plus two stereoisomeric tetrahydrofuran lignans—fragransin B2 (3) and fragransin B1 (4)—was determined ...
Phenolic content, germination percentage, and host preference were compared among 11 seed populat... more Phenolic content, germination percentage, and host preference were compared among 11 seed populations of witchweed (Striga hermonthica (Del.) Benth. # STRHE). Significant differences in germination percentage occurred among the seed populations after preconditioning by their exposure to different durations of warm-moist conditions. Greatest percentage of seed germinated after 8 days of preconditioning. Preconditioning for more than 16 days reduced percentage germination. The host specificity range of witchweed seed populations that parasitized pearl millet [Pennisetum americanum (L.) K. Schum] was broader than were those seed populations that attacked sorghum [Sorghum bicolor (L.) Moench.]. Results of thin-layer chromatography indicated large variations in phenolic content among the witchweed seed populations.
Phytomedicine : international journal of phytotherapy and phytopharmacology, Jan 11, 2018
Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies wit... more Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism. The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe. Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only frag...
This paper describes an analysis of the diversity and chemical toxicity assessment of three chemi... more This paper describes an analysis of the diversity and chemical toxicity assessment of three chemical libraries of compounds from African flora (the p-ANAPL, AfroMalariaDb, and Afro-HIV), respectively containing compounds exhibiting activities against diverse diseases, malaria and HIV. The diversity of the three data sets was done by comparison of the three most important principal components computed from standard molecular descriptors. This was also done by a study of the most common substructures (MCSS keys). Meanwhile, the in silico toxicity predictions were done through the identification of chemical structural alerts using Lhasa's knowledge based Derek system. The results show that the libraries occupy different chemical space and that only an insignificant part of the respective libraries could exhibit toxicities beyond acceptable limits. The predicted toxicities end points for compounds which were predicted to "plausible" were further discussed in the light of a...
Gueria senegalensis is a single species in this genus that belongs to the family Combretaceae and... more Gueria senegalensis is a single species in this genus that belongs to the family Combretaceae and is commonly known in Sudan as GUBBISH. The plant has many medicinal uses in Sudan and other African countries. Secondary metabolites reported from this genus include mainly beta-carboline alkaloids, flavonoids, tannins and other polyphenols (1, 2). Air dried ground leaves of G. senegalensis were extracted using 70% methanol and fractionated sequentially using petroleum ether, chloroform and ethyl acetate. Extracts obtained from G. senegalensis were tested against chloroquine sensitive Plasmodium falciparum NF54 with chromogenic assay involves the biological reduction by viable cells of the tetrazolium compound 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2Htetrazolium (MTS) assay at two different concentrations 10μg/ml and 5μg/ml. The ethyl acetate fraction significantly inhibited the malaria parasite (99%) at the concentration 10μg/ml. In vitro screening o...
Grewia tenax fruits have different ethnopharmacological uses including treatment of hepatic disor... more Grewia tenax fruits have different ethnopharmacological uses including treatment of hepatic disorders, reducing blood lipids profile, antimalarial and for the reversal of anemia (1). The fruits of G. tenax are widely used in Sudan to enrich blood especially for pregnant and lactating women (2). Different authors have attributed the effectiveness of G. tenax fruits to treat iron deficiency anemia (IDA) to its high iron contents (e.g 3), but the quantity of iron reported to be present in the fruits is far less than the amount required to satisfy the daily iron supplementation required for anemic patients, which amounts to 60 mg/day. This prompted us to speculate on the nature of the secondary metabolites present and their free radical scavenging (RSA) activity taking into consideration that the oxidative process is of prime importance to overcome the oxidative haemolysis produced by viral, parasitic infections and/or excessive consumption of drugs (4). However, the relationship betwee...
Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potenti... more Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of Madurella mycetomatis, the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against M. mycetomatis but also against Actinomadura spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propo...
Neglected tropical diseases are major health hazards in developing countries. Annually, up to 30 ... more Neglected tropical diseases are major health hazards in developing countries. Annually, up to 30 million people are affected by either Chagas disease, African trypansomiasis or leishmaniasis, and more than 200 million by malaria. Most of the currently available drugs have drawbacks in terms of toxicity, limited oral availability, development of resistance, or non-affordability. Tropical plants of the arid zones are a treasure chest for the discovery of bioactive secondary metabolites. This study aims to compile Sudanese medicinal plants, validate their antiprotozoal activities, and identify active molecules. We have performed a survey of medicinal plants of Sudan and selected 62 that are being used in Sudanese traditional medicine. From these, we collected materials such as leaves, stem, bark, or fruit. The plant materials were extracted in 70% ethanol and further fractionated by liquid-liquid partitioning using solvents of increasing polarity. This resulted in a library of 235 fractions. The library was tested in vitro against Plasmodium falciparum (erythrocytic stages), Trypanosoma brucei rhodesiense (bloodstream forms), Trypanosoma cruzi (intracellular amastigotes), and Leishmania donovani (axenic amastigotes). Active fractions were also tested for cytotoxicity. Of the 235 fractions, 125 showed growth inhibitory activity >80% at 10 mg/ml, and >50% at 2 mg/ml against at least one of the protozoan parasites. Plasmodium falciparum was the most sensitive of the parasites, followed by T. b. rhodesiense and L. donovani. Only few hits were identified for T. cruzi, and these were not selective. Contrary to expectation based on phylogeny, but in agreement with previous results, a large number of extracts displayed mutual activity against T. brucei and P. falciparum. HPLC-based activity profiling for selected active extracts was performed to identify the bioactive principles. Active compounds identified by dereplication were guieranone A from Guiera senegalensis J.F.Gmel.; pseudosemiglabrin from Tephrosia apollinea (Delile) DC; ellagic acid and quercetin from Terminalia leiocarpa (DC.) Baill.; and catechin, ethyl gallate, and epicatechin gallate from Vachellia nilotica (L.) P.J.H.Hurter & Mabb. Also the extracts of Croton gratissimus var. gratissimus and Cuscuta hyalina Roth ex Schult. exhibited promising antitrypanosomatid activity. This assessment provides a comprehensive overview of Sudanese medicinal plants and supports the notion that they are a potential source of bioactive molecules against protozoan parasites.
The uses of 40 species of the most commonly prescribed medicinal plants in the Dongola Province, ... more The uses of 40 species of the most commonly prescribed medicinal plants in the Dongola Province, Northern Sudan are described.
We present an in vitro susceptibility assay for Madurella mycetomatis hyphae using resazurin for ... more We present an in vitro susceptibility assay for Madurella mycetomatis hyphae using resazurin for endpoint reading. Using this assay, reproducible MICs were obtained for amphotericin B, itraconazole, voriconazole, posaconazole, terbinafine, and micafungin.
A screening of Sudanese medicinal plants for antiprotozoal activities revealed that the chlorofor... more A screening of Sudanese medicinal plants for antiprotozoal activities revealed that the chloroform and water fractions of the ethanolic root extract of Haplophyllum tuberculatum exhibited appreciable bioactivity against Leishmania donovani. The antileishmanial activity was tracked by HPLC-based activity profiling, and eight compounds were isolated from the chloroform fraction. These included lignans tetrahydrofuroguaiacin B (1), nectandrin B (2), furoguaiaoxidin (7), and 3,3′-dimethoxy-4,4′-dihydroxylignan-9-ol (10), and four cinnamoylphenethyl amides, namely dihydro-feruloyltyramine (5), (E)-N-feruloyltyramine (6), N,N′-diferuloylputrescine (8), and 7′-ethoxy-feruloyltyramine (9). The water fraction yielded steroid saponins 11–13. Compounds 1, 2, and 5–13 are reported for the first time from Haplophyllum species and the family Rutaceae. The antiprotozoal activity of the compounds plus two stereoisomeric tetrahydrofuran lignans—fragransin B2 (3) and fragransin B1 (4)—was determined ...
Phenolic content, germination percentage, and host preference were compared among 11 seed populat... more Phenolic content, germination percentage, and host preference were compared among 11 seed populations of witchweed (Striga hermonthica (Del.) Benth. # STRHE). Significant differences in germination percentage occurred among the seed populations after preconditioning by their exposure to different durations of warm-moist conditions. Greatest percentage of seed germinated after 8 days of preconditioning. Preconditioning for more than 16 days reduced percentage germination. The host specificity range of witchweed seed populations that parasitized pearl millet [Pennisetum americanum (L.) K. Schum] was broader than were those seed populations that attacked sorghum [Sorghum bicolor (L.) Moench.]. Results of thin-layer chromatography indicated large variations in phenolic content among the witchweed seed populations.
Phytomedicine : international journal of phytotherapy and phytopharmacology, Jan 11, 2018
Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies wit... more Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism. The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe. Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only frag...
This paper describes an analysis of the diversity and chemical toxicity assessment of three chemi... more This paper describes an analysis of the diversity and chemical toxicity assessment of three chemical libraries of compounds from African flora (the p-ANAPL, AfroMalariaDb, and Afro-HIV), respectively containing compounds exhibiting activities against diverse diseases, malaria and HIV. The diversity of the three data sets was done by comparison of the three most important principal components computed from standard molecular descriptors. This was also done by a study of the most common substructures (MCSS keys). Meanwhile, the in silico toxicity predictions were done through the identification of chemical structural alerts using Lhasa's knowledge based Derek system. The results show that the libraries occupy different chemical space and that only an insignificant part of the respective libraries could exhibit toxicities beyond acceptable limits. The predicted toxicities end points for compounds which were predicted to "plausible" were further discussed in the light of a...
Gueria senegalensis is a single species in this genus that belongs to the family Combretaceae and... more Gueria senegalensis is a single species in this genus that belongs to the family Combretaceae and is commonly known in Sudan as GUBBISH. The plant has many medicinal uses in Sudan and other African countries. Secondary metabolites reported from this genus include mainly beta-carboline alkaloids, flavonoids, tannins and other polyphenols (1, 2). Air dried ground leaves of G. senegalensis were extracted using 70% methanol and fractionated sequentially using petroleum ether, chloroform and ethyl acetate. Extracts obtained from G. senegalensis were tested against chloroquine sensitive Plasmodium falciparum NF54 with chromogenic assay involves the biological reduction by viable cells of the tetrazolium compound 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2Htetrazolium (MTS) assay at two different concentrations 10μg/ml and 5μg/ml. The ethyl acetate fraction significantly inhibited the malaria parasite (99%) at the concentration 10μg/ml. In vitro screening o...
Grewia tenax fruits have different ethnopharmacological uses including treatment of hepatic disor... more Grewia tenax fruits have different ethnopharmacological uses including treatment of hepatic disorders, reducing blood lipids profile, antimalarial and for the reversal of anemia (1). The fruits of G. tenax are widely used in Sudan to enrich blood especially for pregnant and lactating women (2). Different authors have attributed the effectiveness of G. tenax fruits to treat iron deficiency anemia (IDA) to its high iron contents (e.g 3), but the quantity of iron reported to be present in the fruits is far less than the amount required to satisfy the daily iron supplementation required for anemic patients, which amounts to 60 mg/day. This prompted us to speculate on the nature of the secondary metabolites present and their free radical scavenging (RSA) activity taking into consideration that the oxidative process is of prime importance to overcome the oxidative haemolysis produced by viral, parasitic infections and/or excessive consumption of drugs (4). However, the relationship betwee...
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