IN SILICO IDENTIFICATION OF NATURAL PRODUCTS WITH ANTITUBERCULOSIS ACTIVITY FOR THE INHIBITION OF INHA AND ETHR PROTEINS FROM MYCOBACTERIUM TUBERCULOSIS

Abstract

Objective: The rise of Mycobacterium tuberculosis (MT) strains that are resistant to antibiotics poses a serious threat to public health, particularly in middle and low-income countries. The important role of natural products (NPs) in the discovery of new drugs to treat infectious diseases is driving the success of synthetic chemistry in the production of new drugs. In our study, 15 NPs were selected to be investigated for their anti-TB properties by in silico method. Methods: Molecular reverse docking approach to predict the interaction of NPs as a drug lead against the regulatory proteins (InhA, EthR) of MT. For each mycobacterial target, the docking scores/binding free energies were predicted and calculated using AutoDock Vina along with the physicochemical and structural characteristics of the NPs, and they were compared to the established inhibitor (control) drugs. Results: The specific interactions of luteolin, piperine, butein, tiliacorinine against the targets InhA and EthA (-9.1 and-6.7 kcal. mol-1;-9.1 and-8.4 kcal. mol-1;-8.4 and-6.6 kcal. mol-1;-8.3 and-7.6 kcal. mol-1) had significantly superior docking scores compared to controls. Conclusion: Our research proposed these compounds as potent therapeutic agents for the development of anti-tuberculosis medications; however, additional in vitro and in vivo testing is required to confirm their potential as novel therapeutics and mechanisms of action.