Identification of potential Mycolyltransferase Ag85C inhibitors of Mycobacterium tuberculosis H37Rv via Virtual High Throughput Screening and Binding free energy studies

摘要

Tuberculosis (TB) is a deadly disease which causes millions of death annually worldwide. Although TB is treatable but the rise of cases of multidrug-resistant and totally drug-resistant strains of Mycobacterium tuberculosis (Mtb) poses a great challenge to cure TB completely and this situation demands an urgent need for development of potential anti-tubercular drugs. In this regard, the antigen 85C (Ag85C) has emerged as an essential mycobacterial drug target as it plays a central role in synthesizing major components of the inner and outer layers of outer membrane of Mtb. In this research, we have identified four novel potential inhibitors as a potent inhibitor of the Mtb Ag85C from CHEMBL24, MolPort, Zinc and PubChem library by High Throughput Virtual Screening. The results of molecular dynamics show that these compounds bind to Ag85C protein with high stability. The ADMET profiling and pharmacophore analysis indicate that these compounds may act as potential anti-mycobacterial candidates. On the basis of findings our work, we propose that these compounds are novel potential inhibitors of Mtb Ag85C with similar or better properties than the classic inhibitor and they can potentially shorten the treatment duration and may have anti-mycobacterial activity against drug-resistant Mtb strains. (C) 2020 Elsevier Inc. All rights reserved.