Abstract

IN SILICO STUDY OF DELAMANID AGAINST MULTIDRUGRESISTANT TUBERCULOSIS

*Anushka B. Gadhave Deshmukh, Komal P. Miskin, Ms. Sandhya P. Kadam, Dr. Prakash D. Jadhav

Abstract

Tuberculosis (TB) is a leading infectious disease caused by Mycobacterium tuberculosis and is a serious global health threat due to rising multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Delamanid is a novel anti-tubercular nitroimidazole drug developed for the treatment of resistant tuberculosis infections. The present study is aimed at in silico assessment of Delamanid through molecular docking and ADMET analysis to investigate its interaction with the target proteins of Mycobacterium tuberculosis and to predict its pharmacokinetic and toxicity profile. The interaction and binding affinity of Delamanid with Deazaflavin-dependent nitroreductase (DDN) enzyme were determined by carrying out molecular docking studies using computational tools such as PyRx and AutoDock Vina. The docking study revealed a good binding affinity and stable protein-ligand interaction through hydrogen bonding, hydrophobic interactions and van der Waals forces with key amino acid residues present in the active site of the target protein. The various properties of Delamanid were analysed using computational tools such as SwissADME and pkCSM to perform absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. The results indicated favourable pharmacokinetic properties such as good oral absorption, effective tissue distribution, stable metabolism, prolonged elimination half-life, and acceptable drug-likeness properties. The study also found that QT interval prolongation was the main toxicity concern with Delamanid therapy. Overall, the results indicate that delamanid has potent antimycobacterial activity, good pharmacokinetics, and high therapeutic potential for multidrug-resistant tuberculosis. The study underlines the importance of in silico approaches in the current anti-tubercular drug research and supports the continuous development of Delamanid based therapies for management of resistant tuberculosis.

Keywords: Molecular docking, Binding affinity, ADMET analysis, Active sites, In silico study.