Synthesis and biological evaluation of some thiazolylpyrazole derivatives as dual anti-inflammatory antimicrobial agents

The synthesis of a novel series of 4-thiazolylpyrazolyl derivatives is described in the present report. All the newly synthesized compounds were examined for their anti-inflammatory activity using cotton pellet-induced granuloma and carrageenan-induced rat paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), ulcerogenic effect and acute toxicity were also determined. Furthermore, all compounds were evaluated for their in vitro antimicrobial activity against Escherichia coli, Staphylococcus aureus and Candida albicans. A docking pose for compounds 8b, 10a and 10b separately in the active site of the human COX-2 enzyme and DNA-gyrase B was also obtained. The results revealed that compounds 8b, 10a and 10b exhibited good anti-inflammatory activity with no or minimal ulcerogenic effect and good safety margin. Compounds 10a and 10b were found to be the most potent anti-inflammatory agents in the present study. Meanwhile, 10a and 10b displayed higher selective inhibitory activity towards COX-2 compared to indomethacin. Moreover, compounds 10a and 10b exhibited promising antibacterial against both E. coli and S. aureus. Docking studies for 8b, 10a and 10b with COX-2 (PDB ID: 1CX2) and DNA-gyrase B (PDB ID: 1EI1) showed good binding profile.

Graphical abstractThe synthesis of a novel series of 4-thiazolylpyrazolyl derivatives is described. The newly synthesized compounds were examined for their anti-inflammatory activity, inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), ulcerogenic effect and acute toxicity. All compounds were evaluated for their in vitro antimicrobial activity against E. coli, S. aureus and C. albicans. A docking pose for compounds 8b, 10a and 10b separately in the active site of the human COX-2 enzyme and DNA-gyrase B was also obtained. The results revealed that compounds 10a and 10b would represent a fruitful matrix for the development of a new class of dual anti-inflammatory antimicrobial agents.Figure optionsDownload full-size imageDownload as PowerPoint slide