Vol. 2, Issue 2, Part A (2025)

The rapid rise of antimicrobial resistance (AMR) has necessitated the discovery of novel therapeutic agents. In this study, a series of thiazole-based derivatives were designed, synthesized, and evaluated for their antimicrobial activity targeting DNA gyrase, a critical enzyme involved in bacterial DNA replication. The compounds were characterized using NMR, mass spectrometry, and HPLC, ensuring high purity. In vitro testing revealed substantial antimicrobial activity against both Gram-positive and Gram-negative bacteria, with compounds T2 and T4 showing the highest inhibition zones and the lowest minimum inhibitory concentrations (MICs). Molecular docking and molecular dynamics simulations revealed that these compounds, particularly T2, effectively bind to the DNA gyrase enzyme, interacting with key residues in the ATP-binding and DNA-binding sites. The computational findings were consistent with experimental data, confirming the suitability of thiazole derivatives as DNA gyrase inhibitors. This study provides valuable insights into the structure-activity relationship (SAR) of thiazole-based compounds and their potential as novel antibiotics in combating resistant bacterial strains.