Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides
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 t...
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MDPI AG
2020-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/7/1553 |
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| author | Maha S. Almutairi Areej N. Al Suwayyid Amal Aldarwesh Omaima M. Aboulwafa Mohamed I. Attia |
| author_facet | Maha S. Almutairi Areej N. Al Suwayyid Amal Aldarwesh Omaima M. Aboulwafa Mohamed I. Attia |
| author_sort | Maha S. Almutairi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T10:11:12Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T10:11:12Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-c4f5f951394847829280d588bd2700112023-11-16T14:32:35ZengMDPI AGMolecules1420-30492020-03-01257155310.3390/molecules25071553Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamidesMaha S. Almutairi0Areej N. Al Suwayyid1Amal Aldarwesh2Omaima M. Aboulwafa3Mohamed I. Attia4Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Optometry and Visual Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21500, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaThe 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.https://www.mdpi.com/1420-3049/25/7/1553coumarin-4-acetamidenonsteroidal antiestrogensSERMsaromatase inhibitors |
| spellingShingle | Maha S. Almutairi Areej N. Al Suwayyid Amal Aldarwesh Omaima M. Aboulwafa Mohamed I. Attia Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides Molecules coumarin-4-acetamide nonsteroidal antiestrogens SERMs aromatase inhibitors |
| title | Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides |
| title_full | Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides |
| title_fullStr | Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides |
| title_full_unstemmed | Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides |
| title_short | Antiestrogenic Activity and Possible Mode of Action of Certain New Nonsteroidal Coumarin-4-acetamides |
| title_sort | antiestrogenic activity and possible mode of action of certain new nonsteroidal coumarin 4 acetamides |
| topic | coumarin-4-acetamide nonsteroidal antiestrogens SERMs aromatase inhibitors |
| url | https://www.mdpi.com/1420-3049/25/7/1553 |
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