New hybrids of thiazole clubbed with fluorinated benzene: Design, synthesis, spectral, antimicrobial, and molecular docking studies

In this study, we designed, synthesized, and characterized twenty-two new thiazole hybrids with 2,4,6-trifluorobenzene and 6-bromo-2,3-difluorobenzene moieties. The design of the target molecules is based on the molecular hybridization approach. The structures of intermediates (3a and 3b) and thiazole hybrids (4a-4v) were elucidated by 1H NMR, 13C NMR, HRMS,19F-NMR, and FTIR spectroscopic techniques. The inhibitory efficacy of the synthesized compounds was assessed against strains of S. pyogenes, S. aureus, P. aeruginosa, Escherichia coli, A. niger, and C. albicans, expressed in terms of MIC values. Compounds 4a, 4c, 4e, 4 g, 4h, 4j, 4o, 4p, and 4u showed substantial antibacterial effectiveness against several tested bacterial strains, exhibiting the MIC value of 62.5 mu g/mL, compared to typical antibacterial medications such as ciprofloxacin (MIC = 50 mu g/mL) and chloramphenicol (MIC = 50 mu g/mL). Compounds 3b, 4 g, 4h, and 4u outperformed griseofulvin, a standard antifungal drug, with an MFC value of 250 mu g/mL against C. albicans. The in-silico analysis of the highly potent antibacterial compounds 4c, 4 g, 4j, and 4o against S. aureus DNA gyrase (PDB: 2xct) revealed that these compounds formed reasonably stable complexes with DNA gyrase, exhibiting binding affinities of-9.7,-9.6,-9.8, and-9.6 kcal/mol, respectively. In this way, both, docking analysis and antimicrobial activities suggest 4c, 4 g, 4j, and 4o to possess antibacterial activities probably through binding to S. aureus DNA gyrase. These compounds need to be further explored to unravel their antibacterial potentials.