Introduction: Thiadiazole derivatives have emerged as promising candidates for the development of novel antibacterial agents. The integrated QSAR–docking–ADME approach highlights thiadiazole derivatives as promising leads with stronger predicted activity than ciprofloxacin, warranting further In-vitro and In-vivo validation. Materials and Methods: A dataset of thiadiazole derivatives with known antibacterial activity was analyzed. 3D-QSAR using comparative molecular field analysis was performed to identify essential structural features. Docking studies were conducted to predict the binding interactions of selected thiadiazole derivatives with bacterial targets, focusing on key interactions, including hydrogen bonding and hydrophobic contacts Results: The QSAR analysis revealed significant correlations between the structural features of the compounds and their antibacterial activity. The 3D-QSAR analysis, utilizing comparative molecular field analysis, provided insights into the three-dimensional structural requirements for optimal antibacterial activity. Molecular docking studies predicted binding interactions between the thiadiazole derivatives and their potential bacterial targets. The results indicated that ligands 4, 5, 9, and 10 exhibited strong binding affinities, ranging from -8.9 to -9.5 kcal/mol. Ligand 4 demonstrated the highest binding energy (-9.5 kcal/mol) by forming hydrogen bonds and hydrophobic interactions at the E. coli effector site. Discussion: Thiadiazole derivatives showed enhanced predicted antibacterial activity over ciprofloxacin, supported by QSAR correlations and docking interactions. Compounds 4, 5, 9, and 10 exhibited the strongest binding energies, highlighting the scaffold's novelty. Further in-vitro and in-vivo validation remains essential for translational application. Conclusion: The integrated QSAR, docking, and ADME analysis identified thiadiazole derivatives, particularly compounds 4, 5, 9, and 10, as promising antibacterial leads with higher predicted binding affinity than ciprofloxacin. While computational findings provide valuable insights, experimental in vitro and in vivo validation is essential to confirm their therapeutic potential.
Pathak et al. (Mon,) studied this question.