Antibacterial and anti-inflammatory activity of valproic acid-pyrazole conjugates as a potential agent against periodontitis

Dong L., Fang L., Dai X., Zhang J., Wang J., Xu P.

DRUG DEVELOPMENT RESEARCH, vol.83, no.1, pp.131-141, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 83 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1002/ddr.21851
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.131-141
  • Keywords: COX-2, hybrid compounds, RAW264, 7 cells, synthesis, DISCOVERY, DISEASES
  • Ankara Haci Bayram Veli University Affiliated: No


Periodontitis is a serious global concern. Therefore, in the present study, we intend to synthesize novel valproic-acid pyrazole conjugates as a novel agent against periodontitis. The molecules were developed in a facile synthetic route and obtained in excellent yields. The entire set of molecules were screened for antibacterial activity against a battery of micro-organisms responsible for periodontitis such as P. gingivalis, P. intermedia, F. nucleatum, and E. coli, where they exhibit considerable inhibitory activity. The most potent compound among the tested series, compound 7c showed bactericidal activity in the time-kill curve against E. coli. Compound 7c also showed inhibition of NF-kappa B transcriptional activity in LPS-stimulated RAW264.7 cells with IC50 of 19.23 mu M. The effect of compound 7c was also investigated in experimentally induced periodontitis in rats on various indices of oxidative stress (MDA, SOD, and GSH), inflammation (TNF-alpha, IL-1 beta, and IL-6), and apoptosis. It has been found that compound 7c significantly inhibits oxidative stress, inflammation, and apoptosis in a dose-dependent manner. Compound 7c also inhibits the expression of COX-2 and iNOS as shown by western blot analysis.