Search

Background: Malaria is an endemic disease affecting many countries in Tropical regions. In the search for compound hits for the design and/or development of new drugs against the disease, many research teams have resorted to African medicinal plants in order to identify lead compounds. Three-dimensional molecular models were generated for anti-malarial compounds of African origin (from 'weakly' active to 'highly' active), which were identified from literature sources. Selected computed molecular descriptors related to absorption, distribution, metabolism, excretion and toxicity (ADMET) of the phytochemicals have been analysed and compared with those of known drugs in order to access the 'drug-likeness' of these compounds., Results: In the present study, more than 500 anti-malarial compounds identified from 131 distinct medicinal plant species belonging to 44 plant families from the African flora have been considered. On the basis of Lipinski's 'Rule of Five', about 70% of the compounds were predicted to be orally bioavailable, while on the basis of Jorgensen's 'Rule of Three', a corresponding >80% were compliant. An overall drug-likeness parameter indicated that approximately 55% of the compounds could be potential leads for the development of drugs., Conclusions: From the above analyses, it could be estimated that >50% of the compounds exhibiting anti-plasmodial/anti-malarial activities, derived from the African flora, could be starting points for drug discovery against malaria. The 3D models of the compounds have been included as an accompanying file and could be employed in virtual screening.

Background: Drug metabolism and pharmacokinetic (DMPK) assessment has come to occupy a place of interest during the early stages of drug discovery today. Computer-based methods are slowly gaining ground in this area and are often used as initial tools to eliminate compounds likely to present uninteresting pharmacokinetic profiles and unacceptable levels of toxicity from the list of potential drug candidates, hence cutting down the cost of the discovery of a drug., Results: In the present study, we present an in silico assessment of the DMPK profile of our recently published natural products database of 1,859 unique compounds derived from 224 species of medicinal plants from the Cameroonian forest. In this analysis, we have used 46 computed physico-chemical properties or molecular descriptors to predict the absorption, distribution, metabolism and elimination (ADME) of the compounds. This survey demonstrated that about 50% of the compounds within the Cameroonian medicinal plant and natural products (CamMedNP) database are compliant, having properties which fall within the range of ADME properties of >95% of currently known drugs, while >73% of the compounds have ≤2 violations. Moreover, about 72% of the compounds within the corresponding 'drug-like' subset showed compliance., Conclusions: In addition to the previously verified levels of 'drug-likeness' and the diversity and the wide range of measured biological activities, the compounds in the CamMedNP database show interesting DMPK profiles and, hence, could represent an important starting point for hit/lead discovery from medicinal plants in Africa.