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Synthesis, cytotoxicity and in silico study of some novel benzocoumarin-chalcone-bearing aryl ester derivatives and benzocoumarin-derived arylamide analogs

Synthesis, cytotoxicity and in silico study of some novel benzocoumarin-chalcone-bearing aryl... AbstractThe development of new prostate cancer protein receptor cytochrome P450 17A1 inhibitors offers the possibility of generating structures of increased potency. To this end, the chalcone analogs 7 and 8 were prepared from treatment of methyl 3-oxo-3H-benzocoumarin-2-carboxylate (4) with aryl aldehydes. Treatment of 7 and 8 with three anti-inflammatory drugs, flurbiprofen, ketoprofen and ibuprofen, in the presence of POCl3/DMAP gave the ester analogs 9–12. Analogously, treatment of ethyl 3-oxo-3H-benzocoumarin-2-carboxylate (15), prepared previously from 2-hydroxy-1-naphthaldehyde (13) and dimethylmalonate (14), with various arylamines: 4-bromoaniline, 2-amino-6-methylpyridine, amino-antipyrine and 2-amino-5-nitrothiazole, in the presence of potassium tert-butoxide gave the benzocoumarine-3-arylamide analogs. The in vitro cytotoxic activities of 9–12 and 16–19 were evaluated against human prostate cancer cell lines (PC-3) and normal human liver epithelia (WRL-68) by MTT assay. Compounds 10 and 17 were the most active cytotoxic agents among the series against PC-3 cells with IC50 values of 71.35 and 78.25 μg mL–1 with SI values of 3.0 and 4.2, respectively (calculated from the cytotoxicity effects of 10 and 17 on the normal human liver epithelia [WRL-68]). Furthermore, compounds 11 and 12 were tested against breast cancer (HER2 cell lines), prostate cancer (DU-135 cell lines) and MCF-7 but were inactive. Molecular docking studies between the protein receptor CYPP450 17A1 and compounds 10 and 17 revealed that these compounds primarily form hydrophobic interactions with the receptor. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Zeitschrift für Naturforschung B de Gruyter

Synthesis, cytotoxicity and in silico study of some novel benzocoumarin-chalcone-bearing aryl ester derivatives and benzocoumarin-derived arylamide analogs

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Publisher
de Gruyter
Copyright
© 2021 Walter de Gruyter GmbH, Berlin/Boston
ISSN
0932-0776
eISSN
1865-7117
DOI
10.1515/znb-2020-0204
Publisher site
See Article on Publisher Site

Abstract

AbstractThe development of new prostate cancer protein receptor cytochrome P450 17A1 inhibitors offers the possibility of generating structures of increased potency. To this end, the chalcone analogs 7 and 8 were prepared from treatment of methyl 3-oxo-3H-benzocoumarin-2-carboxylate (4) with aryl aldehydes. Treatment of 7 and 8 with three anti-inflammatory drugs, flurbiprofen, ketoprofen and ibuprofen, in the presence of POCl3/DMAP gave the ester analogs 9–12. Analogously, treatment of ethyl 3-oxo-3H-benzocoumarin-2-carboxylate (15), prepared previously from 2-hydroxy-1-naphthaldehyde (13) and dimethylmalonate (14), with various arylamines: 4-bromoaniline, 2-amino-6-methylpyridine, amino-antipyrine and 2-amino-5-nitrothiazole, in the presence of potassium tert-butoxide gave the benzocoumarine-3-arylamide analogs. The in vitro cytotoxic activities of 9–12 and 16–19 were evaluated against human prostate cancer cell lines (PC-3) and normal human liver epithelia (WRL-68) by MTT assay. Compounds 10 and 17 were the most active cytotoxic agents among the series against PC-3 cells with IC50 values of 71.35 and 78.25 μg mL–1 with SI values of 3.0 and 4.2, respectively (calculated from the cytotoxicity effects of 10 and 17 on the normal human liver epithelia [WRL-68]). Furthermore, compounds 11 and 12 were tested against breast cancer (HER2 cell lines), prostate cancer (DU-135 cell lines) and MCF-7 but were inactive. Molecular docking studies between the protein receptor CYPP450 17A1 and compounds 10 and 17 revealed that these compounds primarily form hydrophobic interactions with the receptor.

Journal

Zeitschrift für Naturforschung Bde Gruyter

Published: Apr 27, 2021

Keywords: amide analogs; benzocoumarin; breast cancer; cytotoxicity; ester derivatives; molecular docking study

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