Abstract:
Recent publications have suggested that African medicinal plants and their derived products could be viable source of new and better trypanocidal drugs. Nowadays, in silico methods are often used in drug discovery processes to identify new potential drug leads. In this study, we have developed a small library named Afrotryp, comprising three-dimensional chemical structures of potential trypanocidal compounds derived from medicinal plants in Africa (a total of 321 unique chemical structures). We have predicted the pharmacokinetic properties of the library using Qikprop software and employed the three docking/scoring methods implemented in Molecular Operating Environment Dock Tool to assess the affinity of the library dataset towards the binding site of six selected validated anti-Trypanosoma drug targets. It was observed that about 42% of the compounds contained in the Afrotryp dataset were predicted to show a good overall performance in terms of predicted parameters for absorption, distribution, metabolism, elimination and toxicity properties. Docking calculations identified 15 compounds with lowest theoretical binding energies toward the studied proteins, nine of which are suited for the treatment of stage 2 human African trypanosomiasis, due to their low polar surface area. Analysis of their binding modes gave basis for the observed unique molecular interactions which exist between the Afrotryp dataset and the six studied drug targets. The results lay the foundations for the rational development of novel trypanocidal drugs with improved potency.
