Denis Zofou

AfroDb: a select highly potent and diverse natural product library from African medicinal plants.

Computer-aided drug design (CADD) often involves virtual screening (VS) of large compound datasets and the availability of such is vital for drug discovery protocols. We assess the bioactivity and “drug-likeness” of a relatively small but structurally diverse dataset (containing >1,000 compounds) from African medicinal plants, which have been tested and proven a wide range of biological activities. The geographical regions of collection of the medicinal plants cover the entire continent of Africa, based on data from literature sources and information from traditional healers. For each isolated compound, the three dimensional (3D) structure has been used to calculate physico-chemical properties used in the prediction of oral bioavailability on the basis of Lipinski’s “Rule of Five”. A comparative analysis has been carried out with the “drug-like”, “lead-like”, and “fragment-like” subsets, as well as with the Dictionary of Natural Products. A diversity analysis has been carried out in comparison with the ChemBridge diverse database. Furthermore, descriptors related to absorption, distribution, metabolism, excretion and toxicity (ADMET) have been used to predict the pharmacokinetic profile of the compounds within the dataset. Our results prove that drug discovery, beginning with natural products from the African flora, could be highly promising. The 3D structures are available and could be useful for virtual screening and natural product lead generation programs.

Control of malaria and other vector-borne protozoan diseases in the tropics: enduring challenges despite considerable progress and achievements

Vector-borne protozoan diseases represent a serious public health challenge, especially in the tropics where poverty together with vector-favorable climates are the aggravating factors. Each of the various strategies currently employed to face these scourges is seriously inadequate. Despite enormous efforts, vaccines—which represent the ideal weapon against these parasitic diseases—are yet to be sufficiently developed and implemented. Chemotherapy and vector control are therefore the sole effective attempts to minimize the disease burden. Nowadays, both strategies are also highly challenged by the phenomenon of drug and insecticide resistance, which affects virtually all interventions currently used. The recently growing support from international organizations and governments of some endemic countries is warmly welcome, and should be optimally exploited in the various approaches to drug and insecticide research and development to overcome the burden of these prevalent diseases, especially malaria, leishmaniasis, Human African Trypanosomiasis (HAT), and Chagas disease.

In Vitro Antiplasmodial Activity and Cytotoxicity of Extracts of Selected Medicinal Plants Used byTraditional Healers of Western Cameroon

Medicinal plants play a key role in malaria control in Africa, especially in remote areas where health facilities are limited. In order to assess their acclaimed potentials, eleven extracts were prepared from seven selected plants commonly used in Western Cameroon, and tested both for their antiplasmodial activity and cytotoxicity. The antiplasmodial activity was assessed using Lactate Dehydrogenase Assay (pLDH) and the cytotoxicity estimated on LLC-MK2 monkey kidney epithelial cells. Seven extracts from five different plants were significantly active, with very weak or no cytotoxicity. The Dacryodes edulis leaves showed the highest activity (IC50 of 6.45 μg/mL on 3D7 and 8.2 μg/mL on DD2) followed by the leaves of Vernonia amygdalina (IC50 of 8.72 and 11.27 μg/mL on 3D7 and DD2 resp.) and roots of V. amygdalina (IC50 of 8.72 μg/mL on 3D7), Coula edulis leaves (IC50 of 13.80 μg/mL and 5.79 μg/mL on 3D7 and DD2 resp.), Eucalyptus globulus leaves (IC50 of 16.80 μg/mL and 26.45 μg/mL on 3D7 and DD2) and Cuviera longiflora stem bark (IC50 of 20.24 μg/mL and 13.91 μg/mL on 3D7 and DD2). These findings justify the use of five of the seven plants in malaria treatment by traditional healers of Western Cameroon.

Anti-hyperglycaemic globulins from selected Cucurbitaceae seeds used as antidiabetic medicinal plants in Africa

BackgroundThe recent epidemic of diabetes mellitus (DM) in Africa, coupled with rampant poverty, is an indication of the urgent need to develop new efficacious, cheaper and more available drugs to face this growing public health challenge. A number of plants products among which the protein-rich Cucurbitaceae seeds are commonly used in traditional medicine with increasing acclaimed efficacy against DM. The aim of this study was to analyse and evaluate the hypoglycaemic activity of storage proteins of five species of Cucurbitaceae, which include Telfairia occidentalis, Citrullus lanatus, Lagenaria siceraria, Cucumeropsis mannii and Cucurbita moschata.MethodsThe different families of storage proteins were extracted following differential solubility, and their contents were estimated using the Bradford method. The analysis of these proteins was done by electrophoresis in non-denaturing and denaturing conditions. The evaluation of hypoglycaemic properties of various globulins extracted was performed on male Wistar rats by the oral glucose tolerance test.ResultsThe results showed that among the proteins extracted, globulins constitute the most abundant class of storage proteins in all five species selected. Citrullus lanatus and Cucurbita moschata presented the highest levels of globulin (275.34 and 295.11 mg/g dry matter, respectively). The results of electrophoresis showed that all species possess acidic and neutrals albumins and globulins, with molecular weight of protein subunits ranging from 6.36-44.11 kDa for albumins, 6.5-173.86 kDa for globulins and 6.5-49.66 kDa for glutelins. The 6.36 kDa of albumin subunit protein and the 6.5 kDa of globulin subunit protein were present in all the species. The oral glucose tolerance test showed that the globulins of the seeds of all species except Cucumeropsis mannii caused significant drop in blood sugar (88 – 137.80%, compared to the controls, p<0.05).ConclusionsThese findings showed that the selected Cucurbitaceae seeds contained globulins with significant anti-hyperglycaemic activity. It is therefore highly encouraged to pursue investigations towards development of peptide-drugs and/or phytomedicines from these bioactive proteins which could be used as affordable alternative therapy against DM.

Ten Simple Rules for Organizing a Virtual Conference—Anywhere

1 International Institute of Tropical Agriculture, Nairobi, Kenya, 2 Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom, 3 Department of Computer and Information Sciences, Covenant University, Ota, Nigeria, 4 Institute of Bioinformatics, Johannes Kepler University, Linz, Austria, 5 Moroccan Society for Bioinformatics Institute, Morocco, 6 South African National Bioinformatics Institute, University of the Western Cape, Bellville, South Africa, 7 University of Cape Town, Cape Town, South Africa, 8 University of Notre Dame, South Bend, Indiana, United States of America, 9 Biotechnology Unit, University of Buea, Buea, South West Region, Cameroon, 10 International Livestock Research Institute, Nairobi, Kenya, 11 Biosciences Eastern and Central Africa, Nairobi, Kenya, 12 International Center of Insect Physiology and Ecology, Nairobi, Kenya, 13 Bioinformatics Organization, Hudson, Massachusetts, United States of America, 14 Bioinformatics Team, Center for Development of Advanced Computing, Pune University Campus, Pune, India, 15 Harvard School of Public Health, Boston, Massachusetts, United States of America

Ethnobotanical survey and in vitro antiplasmodial activity of medicinal plants used to treat malaria in Kagera and Lindi regions, Tanzania

Tanzania has over 12,000 plant species, some of which are endemic and have potential to yield useful medicines. This study seeks to document such plants used as traditional medicines for treatment of malaria in Kagera region of northwestern Tanzania and Lindi region in south eastern Tanzania. The study also reports on the antiplasmodial activity against chloroquine-resistant Plasmodium falciparum (Dd2) strain of some of the documented plants using the parasite lactate dehydrogenase method. A total of 108 plant species, among which the families Compositae (14; 12.96%), Fabaceae (12; 11.11%), Euphorbiaceae (8; 7.41%), Melastomataceae (6; 5.56%) and Myrtaceae (4; 3.70%) were documented. Sixteen (16; 44.4%) of 36 extracts from 31 plant species that were tested inhibited malaria parasites growth by more than 50%. Bersema abyssinica stem bark extract was the most active with 86.67% inhibition rate followed by Bridelia micrantha stem bark extract with 71.87% inhibition rate. These results confirm the potential for plants used in traditional medicine to yield active antimalarial compounds. Further in vitro and in vivo screening supported by bioassay-guided isolation of active compounds from plants showing good safety margin is suggested.

Evaluation of the cytotoxic activity of extracts from medicinal plants used for the treatment of malaria in Kagera and Lindi regions, Tanzania

A number of medicinal plants used for treatment of malaria in Tanzania have been documented, but information on their safety and efficacy is still based on traditional knowledge accumulated over years and not on pre-clinical and clinical evaluation. The present study aimed to assess the cytotoxic activity of extracts of selected plant species used for treatment of malaria in Tanzania. Ethanol extracts were evaluated for cytoxicity by using MTT assay on LLC-MK2 cells and by brine shrimp lethality assay. Forty five (93.75%) out of 48 crude extracts assessed using LLC-MK2 cells were non-cytotoxic while three extracts (6.25%) were cytotoxic with CC50

New Antimalarial Hits from Dacryodes edulis (Burseraceae) - Part I: Isolation, In Vitro Activity, In Silico "drug-likeness" and Pharmacokinetic Profiles

The aims of the present study were to identify the compounds responsible for the anti-malarial activity of Dacryoedes edulis (Burseraceae) and to investigate their suitability as leads for the treatment of drug resistant malaria. Five compounds were isolated from ethyl acetate and hexane extracts of D. edulis stem bark and tested against 3D7 (chloroquine-susceptible) and Dd2 (multidrug-resistant) strains of Plasmodium falciparum, using the parasite lactate dehydrogenase method. Cytotoxicity studies were carried out on LLC-MK2 monkey kidney epithelial cell-line. In silico analysis was conducted by calculating molecular descriptors using the MOE software running on a Linux workstation. The “drug-likeness” of the isolated compounds was assessed using Lipinski criteria, from computed molecular properties of the geometry optimized structures. Computed descriptors often used to predict absorption, distribution, metabolism, elimination and toxicity (ADMET) were used to assess the pharmacokinetic profiles of the isolated compounds. Antiplasmodial activity was demonstrated for the first time in five major natural products previously identified in D. edulis, but not tested against malaria parasites. The most active compound identified was termed DES4. It had IC50 values of 0.37 and 0.55 µg/mL, against 3D7 and Dd2 respectively. In addition, this compound was shown to act in synergy with quinine, satisfied all criteria of “Drug-likeness” and showed considerable probability of providing an antimalarial lead. The remaining four compounds also showed antiplasmodial activity, but were less effective than DES4. None of the tested compounds was cytotoxicity against LLC-MK2 cells, suggesting their selective activities on malaria parasites. Based on the high in vitro activity, low toxicity and predicted “Drug-likeness” DES4 merits further investigation as a possible drug lead for the treatment of malaria.

Antimalarial and Other Antiprotozoal Products from African Medicinal Plants

Malaria and other protozoan diseases such as trypanosomiasis and leishmaniasis remain leading public health problems in Africa. Recently, the situation has even been worsened by the emergence and rapid spread of resistance to virtually all drug regiments in current use. It is therefore an urgent need to develop new generations of drugs, which should not only be more efficacious and safe, but also available and affordable, especially to the poor communities of the endemic countries. Traditional herbal medicines have long been used in disease control, and they continue to play a key role in daily health care, especially in remote areas of most endemic countries, where access to modern health facilities is limited. However, the proportions of patients relying on traditional remedies vary widely, depending on cultural and socioeconomic factors. This chapter reviews the current status of phytochemical research for new antiprotozoal products from African medicinal plants. The review summarizes the data available in the literature up to December 2012 and is restricted to plant species with significant activity and that have undergone full phytochemical analysis leading to the isolation of some pure compounds. The activities and the structures of the most prominent molecules are described and succinctly discussed, with particular attention paid to those that have shown cross-activities against two or more diseases.

The needs of biomedical science training in Africa: Perspectives from the experience of young scientists

Biomedical research is a powerful tool for solving health challenges developing regions. The present study aimed at describing the needs of biomedical science training in Africa from the experience of young African scientists at home and in the Diaspora. A total of 107 young scientists were recruited through existing international networks and interviewed via a web-based program, on the current status of biomedical research in their different institutions, as well as the major obstacles faced and their aspirations. This survey revealed that although considerable efforts have been made in strengthening research capacity in Africa, a lot remains to be done. Biomedical research in Africa is seriously hindered by obstacles such as lack of infrastructure, expertise, energy supply, institutional support and financial support from governments. We encourage Applied Research and Public-Private Partnership to foster implementation of research findings into goods and services for public benefit.