Molecular Docking Simulation and ADMET/Pharmacokinetic Screening of Newly Designed 2-(2-(aryl)-4-oxo-4,5-dihydrothiazol-5-yl)acetohydrazides as Potential Antitubercular Agents

Abstract

The in silico approach is a smart strategy to identify the potential of a compound to be biologically active against a target disease and to design a more efficient drug candidate. In this work, in silico molecular docking simulation of twenty two (22) newly designed 2-(2-(aryl)-4-oxo-4,5-dihydrothiazol-5-yl)acetohydrazides against DNA gyrase subunit B (Gyr B) is performed using AutoDock Vina. The majority of the designed molecules were found to have a binding affinity higher than the moxifloxacin standard drug. The top five scaffolds with the highest binding affinity (ranging from −6.5 to −7.0 kcal/mol) were chosen as the lead depending on the better orientation of the pose and H-bond interactions. The ADME and toxicity profiles of the selected scaffolds were assessed through SwissADME and Pro-Tox II, providing valuable insights into their potential safety and efficacy. The chosen compounds had excellent pharmacokinetic characteristics, including low toxicity, good oral bio-availability, and acceptable GI absorption. The results suggest that the title compounds possess significant potential as lead molecules for the development of novel therapeutics against multidrug-resistant tuberculosis, providing valuable insights for medicinal chemists and pharmaceutical professionals to design and synthesize novel drug candidates with improved efficacy.