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

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2022-01-01

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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.

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Kimya, Biyokimya, Biyoinorganik Kimya, Temel Bilimler, Chemistry, Biochemistry, Bioinorganic Chemistry, Natural Sciences, Temel Bilimler (SCI), KİMYA, ORGANİK, Natural Sciences (SCI), CHEMISTRY, CHEMISTRY, ORGANIC, Organik Kimya, Fizik Bilimleri, Organic Chemistry, Physical Sciences, 1,2,4-triazoles, apoptosis, cancer, Carvacrol, in silico studies, mPGES-1, Carvacrol, 1, 2, 4-triazoles, cancer, apoptosis, mPGES-1, in silico studies. ©2022 ACG Publication. All rights reserved

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Demirbolat İ., KULABAŞ N., Gürboğa M., Özakpınar Ö. B., Çiftçi G., Yelekçi K., Liu J., Jakobsson P., DANIŞ Ö., OGAN A., et al., "Synthesis and evaluation of antiproliferative and mPGES-1 inhibitory activities of novel carvacrol-triazole conjugates", Organic Communications, cilt.15, sa.4, ss.356-377, 2022

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