In silico approach towards finding inhibitory effect of phytochemicals on trypanothione reductase in leishmania donovani

Abstract

Problem statement: Leishmaniasis caused by Leishmania sp. is second most dangerous tropical disease without any specified therapeutic system available. Trypanothione reductase plays a key role in survival of the protozoa which can be used as target for Structure based Drug designing. Phytochemicals provides a less toxic and accessible source of chemotherapeutic agents. The study deals with discovery of one such agent against the targeted protein for further Anti-leishmanial drug discovery. Method: An in-silico approach was executed in order topfind out theistructure of the targeted protein and prominent lead compound as it potential inhibitor. Result: The structure of Trypanothione reductase was obtained and validated. It was found to be a compatible model suited for further investigation. The docking studies performed provided Curcumin as the potential chemotherapeutic agent giving a high binding energy of -7.9 kcal/mol. The analogues of curcumin presented higher binding energy than base compound. Further ADME/T tests suggested two analogues to be prevalent for further study with binding energy of -11.0 kcal/mol and -8.8 kcal/mol.