Synthesis and evaluation of antiproliferative and mPGES-1 inhibitory activities of novel carvacrol-triazole conjugates


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Demirbolat İ., KULABAŞ N., Gürboğa M., Özakpınar Ö., Çiftçi G., Yelekçi K., ...More

Organic Communications, vol.15, no.4, pp.356-377, 2022 (ESCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 4
  • Publication Date: 2022
  • Doi Number: 10.25135/acg.oc.142.2212.2651
  • Journal Name: Organic Communications
  • Journal Indexes: Emerging Sources Citation Index (ESCI), Scopus, Academic Search Premier, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.356-377
  • Keywords: 1,2,4-triazoles, apoptosis, cancer, Carvacrol, in silico studies, mPGES-1
  • Marmara University Affiliated: Yes

Abstract

Some novel triazole-bearing acetamide derivatives 9-26 were synthesized starting from carvacrol. All synthesized compounds were characterized by FTIR, 1H-NMR, 13C-NMR and MS data. 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 chronic myelogenous leukemia K562, human neuroblastoma SH-SY5Y cell lines) were evaluated by MTT assay. Compounds were also tested on mouse embryonic fibroblast cells (NIH/3T3) to determine selectivity. Eighteen target compounds 9-26 were screened for their mPGES-1 and COX-1/2 inhibitory activities. Of these compounds, 26 (KUC16D425) showed the highest mPGES-1 inhibition at 10 µM. This compound has also been observed to induce apoptosis and inhibit cell migration in MCF-7 cells. In silico molecular docking calculations were performed to understand the binding interactions of compounds with target proteins. ADMET predictions were also done to evaluate drug-like properties of the novel compounds.