Zhaochang Liang, Yuping Huang, Shiben Wang and Xianqing Deng* Pages 1020 - 1030 ( 11 )
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 by1H NMR, 13C NMR and HRMS. In vitro LPS-induced TNF-α model and in vivo xylene-induced ear-edema model were used to evaluate their antiinflammatory 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- α at the concentration of 20 µg/mL Compounds 5i, 6b, and 7b had comparable in vivo antiinflammatory 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 µg/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.
Anti-inflammatory, antimicrobial, pyrazole, (thio) semicarbazide, TNF-α, dexamethasone.
Medical College, Jinggangshan University, No 28, Xueyuan Road, Ji'an, 343009, Jiangxi, Department of Biochemistry and Molecular Biology, Gannan Medical College, Ganzhou, School of Pharmacy, Liaocheng University, LiaoCheng, 252059, Shandong, Medical College, Jinggangshan University, No 28, Xueyuan Road, Ji'an, 343009, Jiangxi