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

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 mu M. 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.