Insights of ligand-based virtual screening in molecular docking and dynamics analysis of coumarin benzamides derivatives against Leishmaniasis

Leishmaniasis is a neglected tropical disease that affects approximately 18 countries, resulting in around 54,000 cases annually. Brazil is responsible for approximately 76% of cases associated with cutaneous leishmaniasis, with Leishmania major being one of the main causes of the disease's incidence. Coumarins are compounds of natural origin with several biological applications, widely used in synthesis for analysis as potential inhibitors of biological targets. This study aims to evaluate the potential effect of the derivatives against leishmaniasis through the analysis of interactions formed via molecular docking studies, where ligands CBD1-5 were evaluated against the target receptor. Then, all the complexes were subjected to stability tests over 200 ns, utilizing the molecular dynamics technique. Through ADMET studies, it was shown that the compounds present high cellular permeability, resulting in improved oral bioavailability. This study is an initial step that aims to rank and elucidate possible mechanisms of action against Leishmania major.