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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

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

Author(s): Zhaochang Liang, Yuping Huang, Shiben Wang and Xianqing Deng*

Volume 16, Issue 9, 2019

Page: [1020 - 1030] Pages: 11

DOI: 10.2174/1570180816666190325163117

Abstract

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.

Keywords: Anti-inflammatory, antimicrobial, pyrazole, (thio) semicarbazide, TNF-α, dexamethasone.

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