Design synthesis and biological evaluation of thiophene 2-pentafluoro benzamide derivatives as antitubercular agent

Abstract

Tuberculosis, a major contagious air-borne disease, killing millions in a year. Many of the existing anti-tubercular drugs have acquired bacterial resistance. Though they are highly bactericidal but, later on due to several factors like poor patient compliance, incomplete therapy, etc. leading to treatment relapse. This enables researcher to focus on identifying new leads utilizing structure-based drug design which plays a crucial role in drug development. The mycolic acid synthesized by Pks 13 is identified as a perfect target and hence a series of molecules were designed and the best fit ligands with a least energy were picked and analysed for Insilco bioactivity and drug likeness. Five best docked Molecules satisfied the Lipinski rule of five, namely the number of hydrogen bond donors, acceptors, log P, total polar surface area and the number of rotatable bonds. The bioactivity was found to be moderate to excellent against the receptor. The target molecules were synthesised via amino esters to yield pentafluorinated thiophene derivatives. Among the series, molecule 12 was found to be more potent when tested for antitubercular activity by Microplate Alomar blue assay technique.