Academic Journal
CYP1-Activation and Anticancer Properties of Synthetic Methoxylated Resveratrol Analogues
| العنوان: | CYP1-Activation and Anticancer Properties of Synthetic Methoxylated Resveratrol Analogues |
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| المؤلفون: | Ketan C. Ruparelia, Keti Zeka, Kenneth J. M. Beresford, Nicola E. Wilsher, Gerry A. Potter, Vasilis P. Androutsopoulos, Federico Brucoli, Randolph R. J. Arroo |
| المصدر: | Molecules, Vol 29, Iss 2, p 423 (2024) |
| بيانات النشر: | MDPI AG |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | stilbenes, CYP1A1, CYP1B1, prodrug, Wittig reaction, breast cancer, Organic chemistry, QD241-441 |
| الوصف: | Naturally occurring stilbenoids, such as the ( E )-stilbenoid resveratrol and the ( Z )-stilbenoid combretastatin A4, have been considered as promising lead compounds for the development of anticancer drugs. The antitumour properties of stilbenoids are known to be modulated by cytochrome P450 enzymes CYP1A1 and CYP1B1, which contribute to extrahepatic phase I xenobiotic and drug metabolism. Thirty-four methyl ether analogues of resveratrol were synthesised, and their anticancer properties were assessed, using the MTT cell proliferation assay on a panel of human breast cell lines. Breast tumour cell lines that express CYP1 were significantly more strongly affected by the resveratrol analogues than the cell lines that did not have CYP1 activity. Metabolism studies using isolated CYP1 enzymes provided further evidence that ( E )-stilbenoids can be substrates for these enzymes. Structures of metabolic products were confirmed by comparison with synthetic standards and LC-MS co-elution studies. The most promising stilbenoid was ( E )-4,3′,4′,5′-tetramethoxystilbene (DMU212). The compound itself showed low to moderate cytotoxicity, but upon CYP1-catalysed dealkylation, some highly cytotoxic metabolites were formed. Thus, DMU212 selectively affects proliferation of cells that express CYP1 enzymes. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1420-3049 |
| Relation: | https://www.mdpi.com/1420-3049/29/2/423; https://doaj.org/toc/1420-3049; https://doaj.org/article/1a835ddfa853407ea178b403a70816a8 |
| DOI: | 10.3390/molecules29020423 |
| الاتاحة: | https://doi.org/10.3390/molecules29020423 https://doaj.org/article/1a835ddfa853407ea178b403a70816a8 |
| رقم الانضمام: | edsbas.CEDAA973 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14203049 |
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| DOI: | 10.3390/molecules29020423 |