An in-silico design of a novel ursodeoxycholic acid analogue for helminthiasis therapy

Helminths, elongated insects, infect millions of humans worldwide, affecting 25 % of the population worldwide. Anthelmintic drugs treat helminthic-related illnesses, but resistance occurs when drug effectiveness decreases in receptive parasite populations. Fumarate respiration, an electron transport chain in anaerobic bacteria, influences adult parasite energy metabolism in hosts. Consisting of complex I, rhodoquinone, and complex II, with complex II being a promising target for study. The study aims to develop new chemical entities using FDA approved drugs through computer aided drug design approach for the treatment of helminthic infections. 2637 FDA-approved drugs have been downloaded from the drug data bank, and molecules have been subjected to molecular docking studies against MRFR protein (PDB ID: 3VR8) to understand protein-drug interaction. From the docking and MMGBSA score Ursodeoxycholic acid was identified as “Top HIT molecule”. Schrödinger’s ligand designer suite is used to derivatise the Ursodeoxycholic acid to convert the unfavourable region to favourable region. A study involving 143 compounds which is derivatise by ligand designer was subjected to docking with the target protein MRFR. The "lead molecule 1" showed a higher docking score than the "Top HIT molecule" Ursodeoxycholic acid, indicating the effectiveness of the designed novel molecules. A study of the "lead molecule 1” showed promising results in in-silico helminthic inhibition, suggesting potential for developing new anthelmintic agents.