دورية أكاديمية
New Dual Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 and 2 Based on Deoxycholic Acid: Design, Synthesis, Cytotoxicity, and Molecular Modeling
| العنوان: | New Dual Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 and 2 Based on Deoxycholic Acid: Design, Synthesis, Cytotoxicity, and Molecular Modeling |
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| المؤلفون: | Oksana V. Salomatina, Tatyana E. Kornienko, Alexandra L. Zakharenko, Nina I. Komarova, Chigozie Achara, Jóhannes Reynisson, Nariman F. Salakhutdinov, Olga I. Lavrik, Konstantin P. Volcho |
| المصدر: | Molecules, Vol 29, Iss 3, p 581 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Organic chemistry |
| مصطلحات موضوعية: | deoxycholic acid, oxirane, thiols, TDP1 inhibitor, TDP2 inhibitor, cancer, Organic chemistry, QD241-441 |
| الوصف: | Deoxycholic acid derivatives containing various heterocyclic functional groups at C-3 on the steroid scaffold were designed and synthesized as promising dual tyrosyl-DNA phosphodiesterase 1 and 2 (TDP1 and TDP2) inhibitors, which are potential targets to potentiate topoisomerase poison antitumor therapy. The methyl esters of DCA derivatives with benzothiazole or benzimidazole moieties at C-3 demonstrated promising inhibitory activity in vitro against TDP1 with IC50 values in the submicromolar range. Furthermore, methyl esters 4d–e, as well as their acid counterparts 3d–e, inhibited the phosphodiesterase activity of both TDP1 and TDP2. The combinations of compounds 3d–e and 4d–e with low-toxic concentrations of antitumor drugs topotecan and etoposide showed significantly greater cytotoxicity than the compounds alone. The docking of the derivatives into the binding sites of TDP1 and TDP2 predicted plausible binding modes of the DCA derivatives. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1420-3049 42859786 |
| Relation: | https://www.mdpi.com/1420-3049/29/3/581; https://doaj.org/toc/1420-3049 |
| DOI: | 10.3390/molecules29030581 |
| URL الوصول: | https://doaj.org/article/f7a6940d786f428597863fdfcc30635e |
| رقم الأكسشن: | edsdoj.f7a6940d786f428597863fdfcc30635e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14203049 42859786 |
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| DOI: | 10.3390/molecules29030581 |