| Summary: | The preparation of certain 2-(2-oxo-2<i>H</i>-chromen-4-yl)-<i>N</i>-substituted acetamides <b>IIIa–h</b> was planned as a step in the development of new modified nonsteroidal antiestrogens. The purity of target compounds <b>IIIa–h</b> was checked by thin-layer chromatography (TLC), and their structures were confirmed using various spectroscopic tools including IR, <sup>1</sup>H-NMR, <sup>13</sup>C-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 <b>IIIb</b> proved the most active against MCF-7 cells, with an IC<sub>50</sub> value of 0.32 μM. The results of an analysis of in vitro antiestrogenic activity indicated that only compound <b>IIIb</b> exhibited antiestrogenic activity; its IC<sub>50</sub> value of 29.49 μM was about twice as potent as that of the reference compound, MIBP. The aromatase activity was evaluated for the synthesized target compounds <b>IIIa–g</b> and the intermediates <b>Ib</b> and <b>IIa</b>. A significant aromatase inhibition was observed for the intermediate <b>Ib</b> and compound <b>IIIe</b>, with IC<sub>50</sub> values of 14.5 and 17.4 μM, respectively. Compound <b>IIIb</b>, 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.
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