In-silico ANALYSIS OF THE INHIBITORY ACTIVITIES OF NOVEL AZO DERIVATIVES OF BENZIMIDAZOLE ON Mycobacterium tuberculosis DPRE1

Abstract

DprE1 inhibitors were analysed by high-throughput screening against mycobacterial cells, which produce a new class of compounds known as anti-tubercular agents. DprE1 is a fundamental mycobacterial enzyme that is responsible for the synthesis of mycobacterial cell walls. DprE1 is identified as a new target and the compounds inhibiting this target are proved to be active against such mycobacterial cells that are resistant to conventionally available marketed TB drugs. In this interest, a set of some new azo benzimidazole, prepared by condensing diazonium derivatives of benzimidazole with different suitable aromatic derivatives, were used as ligand against Mycobacterium tuberculosis DprE1 receptor. For this purpose, the crystal structure of Mycobacterium tuberculosis DprE1 in complex with the non-covalent inhibitor QN118 (PDB ID: 4P8N, 1.79 Å X-ray resolution) was retrieved from the RCSB Protein Database and used as the target. All the compounds were firmly inhibited by filling the active sites in the model with low energy values. The Present study backed that the anti-TB compounds designed by Mohanty et al. (2018) justify their in silico inhibitory property on DprE1. So, these compounds can be of clinical importance against specific diseases that may be related to the protein DprE1.