Designing of Nitroimidazole Derivatives as a Promising Target for Treatment of Tuberculosis

Abstract

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, with high level of mortality worldwide, currently with approximately 10 million cases of tuberculosis. These rate of incidence are due to several factors such as bacterial resistance, AIDS, latent tuberculosis that reoccur in patient. Deazaflavin dependent nitroreductase (Ddn) is an emerging target in the field of antitubercular agent. Ddn catalyses the reduction of nitroimidazoles resulting in intra-cellular release of lethal reactive nitrogen species. Nitroimidazole class drug- delamanid and pretonamid are used in the treatment of MDR-TB. In this present study, 26 new nitroimidazole derivatives were designed and docked into Ddn enzyme. In docking study, compounds 3, 5, 15, 16, 17, 18 and 21 showed similar interaction with amino acid residues such as Tyr 65, Ser 78, Tyr 136 as pretonamid reference drug and highest docking score and better ADMET compatibility. The ADMET prediction docking study of new designed compound revealed that the compounds 3, 16, 17 and 21 showed good binding with Ddn. In future it may be good and effective lead for development of antitubercular agent.