Synthesis and Biological Evaluation of Some Pyrazole Derivatives, Containing (Thio) Semicarbazide, as Dual Anti-Inflammatory Antimicrobial Agents

Background: Several series of pyrazole derivatives containing (thio) semicarbazide (4a-4h, 5a-5l, 6a-6f, 7a-7c) were designed and synthesized to screen dual inflammatory and antimicrobial activities. Methods: The products were characterized by H-1 NMR, C-13 NMR and HRMS. In vitro LPS-induced TNF-alpha model and in vivo xylene-induced ear-edema model were used to evaluate their anti-inflammatory activity. Their in vitro antimicrobial activities were evaluated using a serial dilution method against several gram-positive strains, gram-negative strains and a fungi strain. Results: Bioassays indicated that most of the compounds markedly inhibited the expression of TNF-alpha at the concentration of 20 mu g/mL Compounds 5i, 6b, and 7b had comparable in vivo anti-inflammatory activity to the reference drug dexamethasone at the dose of 50 mg/kg. In addition, several compounds showed antimicrobial activity against different strains, and compounds 5g and 5h exhibited potent inhibitory activities with the MIC value of 8 mu g/mL against the Streptococcus pneumoniae CMCC 31968 and Staphylococcus aureus CMCC 25923, respectively. Compound 7b, which exhibited both anti-inflammatory and antimicrobial activities, should be studied as it is or after derivatization. Conclusion: It can be concluded that pyrazoles, with (thio)-semicarbazone moieties, have the potential to be developed into new anti-inflammatory agents.