Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity

Bulbul B., Ding K., Zhan C., Ciftci G., YELEKÇİ K., Gurboga M., ...More

MOLECULAR DIVERSITY, vol.27, no.5, pp.2185-2215, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 5
  • Publication Date: 2023
  • Doi Number: 10.1007/s11030-022-10551-0
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.2185-2215
  • Keywords: 1,2,4-Triazole, Atropisomer, Diastereotope, X-ray diffraction, Cancer, Angiogenesis, mPGES-1, Cytotoxicity, PROSTAGLANDIN-E SYNTHASE-1, ANTIINFLAMMATORY ACTIVITY, HYBRIDS SYNTHESIS, BETA-CATENIN, TUMOR-GROWTH, DERIVATIVES, COX-2, DISCOVERY, DESIGN, ANTIBACTERIAL
  • Marmara University Affiliated: Yes


Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46-68.76 mu M, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 mu M. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment.