Design, Synthesis, and Antimicrobial Evaluation of Novel Pyrazole–Thiazole Derivatives as Potential Broad-Spectrum Agents
摘要
In this work, a new series of pyrazole–thiazole derivatives was obtained through the functional transformation of the enaminonitrile intermediate. The designed compounds include fused pyridine, benzothiazole, benzimidazole, pyrano-pyrazole, pyrano-pyrimidine, and coumarin-linked scaffolds, representing structurally diverse systems with potential biological relevance. All synthesized derivatives were screened for their antimicrobial activity; however, molecular docking investigations were conducted only for the most potent compounds identified in the biological assay. Several compounds, 6, 7, 8, and 11, demonstrated strong and broad-spectrum antibacterial activity against Gram-positive S. aureus, Gram-negative E. coli, and the fungal strain C. albicans, according to the results of the biological screening. Inhibition zones occasionally exceeded those of reference medications, and minimum inhibitory concentrations as low as 3.125 µg/mL were observed. Structure–activity relationship analysis revealed that the presence of strong electron-withdrawing groups such as nitrile (–C ≡ N), nitro (–NO2), heteroaromatic nitrogen atoms (pyridine, pyrimidine), and benzothiazole/benzimidazole heteroatoms plays a key role in enhancing the antimicrobial potency of compounds 6, 7, 8, and 11. Molecular docking studies further supported strong interactions of active compounds with microbial targets, displaying higher binding affinities than standard antibiotics such as chloramphenicol and cephalothin. Overall, the findings highlight these newly synthesized heterocyclic scaffolds as promising candidates for the development of next-generation antimicrobial agents against drug-resistant pathogens.