Alkaloids and Quinolones as potential MtbTopI inhibitors: An in-silico discovery using ADME studies and molecular dynamics simulation

Abstract

Abstract Mycobacterium tuberculosis (M.tb), the causative agent of Tuberculosis, threats human lives more than any other infectious diseases worldwide. Despite of various developed drugs against M.tb, lack of an efficient therapeutic has led to continuous formulation of new drugs against the disease. The bacteria's specific adaptations to achieve drug resistance operate as a defensive mechanism, thereby making the development of anti-mycobacterial drugs particularly complicated. Therefore, targeting new receptors in the bacteria to develop a potential drug is recommended. In this study, a pool of alkaloid and quinolone compounds have been screened against the M.tb Topoisomerase I receptor. The prime function of MtbTopI in mycobacterium is to maintain DNA topology and regulate the torsional stress during DNA replication. Targeting MtbTopI can not only disrupt DNA structure, but also lead to restricted growth and ultimately death of the pathogen. A total of 257 alkaloids and 1515 quinolones were screened in silico against the receptor to find compounds able to inhibit the growth of Mycobacterium tuberculosis. One alkaloid and two quinolones were eventually found as potential inhibitors of MtbTopI.