Design, Synthesis, In Vitro Evaluation and Docking Studies of Pyrazole-Thiazole Hybrids as Antimicrobial and Antibiofilm Agents

In the present study, a series of novel pyrazole-thiazole hybrids (4a-l) were designed, synthesized and assessed for their in vitro antimicrobial activity against both Gram-positive and Gram-negative pathogenic bacterial and fungal strains. Compounds derived from p-CH3 phenyl (4b), p-Br phenyl (4g), 8-bromocoumarinyl (4k), and 6,8-dibromocoumarinyl (4l) exhibited promising inhibitory activity against the tested bacterial strains with minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) spectrum of 1.9/7.8 mu g/mL to 3.9/7.8 mu g/mL. The compounds with p-CH3 phenyl (4b), p-OCH3 phenyl (4c), benzo[f]coumarinyl (4j), 8-bromocoumarinyl (4k) substitutions showed their inhibitory potency against various Candida strains with MIC/minimum fungicidal concentration (MFC) values of 3.9/7.8 mu g/mL. Also, anti-biofilm and toxicity profile of the compounds was also tested. The biofilm inhibition results revealed that the compound 4j exhibited promising activity with an IC50 value of 11.8 mu M against S. aureus MTCC 96, while 4k showed significant activity against S. aureus MLS16 MTCC 2940, K. planticola MTCC 530 and C. albicans MTCC 3017 with IC50 values of 12, 14 and 16 mu M, respectively. The present study has emphasized that thiazole-pyrazole hybrids with benzothiazole and coumarin scaffolds can be a novel and potent class of molecules with potential biological activities.