Abstract

MOLECULAR DOCKING STUDIES OF CHROMENE ANALOGUES ON TRYPANOTHIONE REDUCTASE FOR TARGETING LEISHMANIASIS

Jeevan Patra*, Harshdeep Garewal and Nripendra Singh Sengar

Abstract

Leishmaniasis parasitic disease is one of the neglected and are an epidemic in various countries, and these parasites are developing resistance against drugs available in market. Thus, discovery and development of new potent drugs against Leishmaniasis is an open area of investigation for a researcher. To perform these challenges, a series of chromene analogues have been designed and docked into the active site of Trypanothione Reductase (TryR) enzyme required to balance redox of the parasite. The potent ligands were screened (hits) based on the search algorithm MolDock score by docking and subjected to ADMET test to identify the suitable lead compound against leishmaniasis. In total 18 compounds out of which compounds 11, 12, 14 were found to be the most active among the tested compounds. Although the compounds showing moderate antileishmanial activity, they identifies a chemical space to design and develop drugs based on these chromene derivatives against the Leishmania parasite. Toxicology studies revealed compound 14 as a nontoxic compound. Molecular Docking studies showed that compound 14 showed greater affinity towards TryR due to presence of hydrogen bonding formation exactly at aforementioned positions. In this study we reported the molecular interaction mechanism between chromene analogues and TRP using molecular docking and identified the compound 14 as potential lead compound against leishmaniasis. Further study on compound 14 analogues, lead optimization and validation such as increasing in bond length or replacing halogen to –NO2, addition of bis-chromene, naphthyl etc. may lead to novel drug as lead compounds against Leishmaniasis.

Keywords: Trypanothione Reductase, Molegro Virtual Docker 4.0, ADMET Test, Drug Likenesses, Protein Data Bank: 2JK6.