Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides
| Autor: | Areej N Al Suwayyid, Mohamed I. Attia, Amal Aldarwesh, Maha S. Almutairi, Omaima M. Aboulwafa |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cell Survival
Pharmaceutical Science 010501 environmental sciences 01 natural sciences Article Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound nonsteroidal antiestrogens 0302 clinical medicine lcsh:Organic chemistry Coumarins Cell Line Tumor Drug Discovery Acetamides Cytotoxic T cell Humans Physical and Theoretical Chemistry Aromatase Cytotoxicity Mode of action IC50 0105 earth and related environmental sciences biology Dose-Response Relationship Drug Molecular Structure Aromatase Inhibitors Organic Chemistry Estrogen Antagonists Antiestrogen Coumarin In vitro chemistry Chemistry (miscellaneous) 030220 oncology & carcinogenesis coumarin-4-acetamide biology.protein Molecular Medicine SERMs Nuclear chemistry |
| Zdroj: | Molecules Molecules, Vol 25, Iss 1553, p 1553 (2020) Volume 25 Issue 7 |
| ISSN: | 1420-3049 |
| Popis: | The preparation of certain 2-(2-oxo-2H-chromen-4-yl)-N-substituted acetamides IIIa&ndash h was planned as a step in the development of new modified nonsteroidal antiestrogens. The purity of target compounds IIIa&ndash h was checked by thin-layer chromatography (TLC), and their structures were confirmed using various spectroscopic tools including IR, 1H-NMR, 13C-NMR, and MS spectroscopy. Viability tests were applied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effect of the synthesized compounds against two breast cancer cell lines, MCF-7 and MDA-MB-231. Compound IIIb proved the most active against MCF-7 cells, with an IC50 value of 0.32 &mu M. The results of an analysis of in vitro antiestrogenic activity indicated that only compound IIIb exhibited antiestrogenic activity its IC50 value of 29.49 &mu M was about twice as potent as that of the reference compound, MIBP. The aromatase activity was evaluated for the synthesized target compounds IIIa&ndash g and the intermediates Ib and IIa. A significant aromatase inhibition was observed for the intermediate Ib and compound IIIe, with IC50 values of 14.5 and 17.4 &mu M, respectively. Compound IIIb, namely 7-methoxy-4-(2-oxo-2-(piperidin-1-yl)ethyl)-2H-chromen-2-one, could be used as an antiestrogen and/or cytotoxic agent with selective activity against tumor cells. |
| Databáze: | OpenAIRE |
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