New pyrazolyl pyrazole–thiazole hybrids: synthesis, spectral, antimicrobial analysis and molecular docking studies
摘要
A series of thirteen novel pyrazolyl pyrazole–thiazole hybrids (5a–5k, 6, 7) and two pyrazolyl-pyrazole hybrids (8, 9) were designed, synthesized, and structurally confirmed by 1H-NMR, HRMS, FT-IR, 13C-NMR, 2D-NOESY spectroscopic techniques, and elemental analysis. The pyrazole–thiazole hybrids (5a–5k) were obtained by the Hantzsch reaction between the thiosemicarbazone 4 and 2-bromo-1-phenylethanone derivatives in ethanol at ambient temperature. The antimicrobial potency of synthesized hybrids was evaluated by inspecting them against S. aureus, E. coli, S. pyogenes, P. aeruginosa, C. albicans and A. niger pathogens. Most of the compounds (3, 5a, 5d, 5e, 5j, and 9) exhibited significant antibacterial effectiveness with a MIC value of 62.5 µg/mL as compared with positive control chloramphenicol and ciprofloxacin (MIC = 50 µg/mL). Additionally, pyrazole–thiazole hybrids 5g, 5h, and 7 proved their significant antifungal potential with an MFC value of 250 µg/mL, in contrast, compounds 5b, 5e, 5f, 5k, and 6 exhibited equal antifungal potential against C. albicans in comparison with positive control standard antifungal agent Griseofulvin (MFC=500 µg/mL). The study on molecular docking demonstrated that the compounds 5a, 5d, 5e, and 5j bind the nitrogenous bases of DNA gyrase of the targeted 2XCT protein with the binding affinity of − 9.3, − 9.6, − 9.3, and − 9.3 kcal/mol, respectively. Our synthesis, antimicrobial analysis, and molecular docking study suggested that the pyrazole–thiazole hybrids 5a, 5d, 5e, and 5j provided an important reference for further progression in the antibacterial drugs.
Graphical abstract