Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants

Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B beta, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Guner-Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (similar to 400 compounds from African medicinal plants), along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising similar to 1,500 published naturally occurring plant-based compounds from around the world). Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa's expert knowledge-based system (Derek), showing that only an insignificant proportion of the promising anticancer agents would be likely showing high toxicity profiles. A diversity study of the two datasets, carried out using the analysis of principal components from the most important physicochemical properties often used to access drug-likeness of compound datasets, showed that the two datasets do not occupy the same chemical space

Molecular Modeling of Potential Anticancer Agents from African Medicinal Plants

Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of similar to 400 compounds from African medicinal plants that have shown in vitro and/or in vivo anticancer, cytotoxic, and antiproliferative activities has been explored. To verify potential binding to anticancer drug targets, the interactions between the compounds and 14 selected targets have been analyzed by in silk modeling. Docking and binding affinity calculations were carried out, in comparison with known anticancer agents comprising similar to 1 500 published naturally occurring plant-based compounds from around the world. The results reveal that African medicinal plants could represent a good starting point for the discovery of anticancer drugs. The small data set generated (named AfroCancer) has been made available for research groups working on virtual screening

Molecular Modeling of Potential Anticancer Agents from African Medicinal Plants

Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or <i>in silico</i> virtual screening methods are often used in lead/hit discovery protocols. In this study, the “drug-likeness” of ∼400 compounds from African medicinal plants that have shown <i>in vitro</i> and/or <i>in vivo</i> anticancer, cytotoxic, and antiproliferative activities has been explored. To verify potential binding to anticancer drug targets, the interactions between the compounds and 14 selected targets have been analyzed by <i>in silico</i> modeling. Docking and binding affinity calculations were carried out, in comparison with known anticancer agents comprising ∼1 500 published naturally occurring plant-based compounds from around the world. The results reveal that African medicinal plants could represent a good starting point for the discovery of anticancer drugs. The small data set generated (named AfroCancer) has been made available for research groups working on virtual screening