Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities
| العنوان: | Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities |
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| المؤلفون: | Albena T. Dinkova-Kostova, Renee Risingsong, Nanjoo Suh, Michael B. Sporn, Paul Talalay, Katherine K. Stephenson, Charlotte R. Williams, Darlene B. Royce, Tadashi Honda, Karen T. Liby, Gordon W. Gribble, Chitra Sundararajan |
| المصدر: | Molecular Cancer Therapeutics. 6:2113-2119 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Male, Cancer Research, Apoptosis, Pharmacology, Nitric Oxide, Mice, chemistry.chemical_compound, Cell Line, Tumor, Betulinic acid, NAD(P)H Dehydrogenase (Quinone), Animals, Humans, Potency, Betulinic Acid, Cell Proliferation, bcl-2-Associated X Protein, Inflammation, chemistry.chemical_classification, biology, Chemistry, Macrophages, Fibroblasts, Antineoplastic Agents, Phytogenic, Triterpenes, In vitro, Nitric oxide synthase, Enzyme, Oncology, Biochemistry, Cytoprotection, Cell culture, Cancer cell, biology.protein, Pentacyclic Triterpenes |
| الوصف: | Betulinic acid (BA), a pentacyclic triterpene isolated from birch bark and other plants, selectively inhibits the growth of human cancer cell lines. However, the poor potency of BA hinders its clinical development, despite a lack of toxicity in animal studies even at high concentrations. Here, we describe six BA derivatives that are markedly more potent than BA for inhibiting inducible nitric oxide synthase, activating phase 2 cytoprotective enzymes, and inducing apoptosis in cancer cells and in Bax/Bak−/− fibroblasts, which lack two key proteins involved in the intrinsic, mitochondrial-dependent apoptotic pathway. Notably, adding a cyano-enone functionality in the A ring of BA enhanced its cytoprotective properties, but replacing the cyano group with a methoxycarbonyl strikingly increased potency in the apoptosis assays. Higher plasma and tissue levels were obtained with the new BA analogues, especially CBA-Im [1-(2-cyano-3-oxolupa-1,20(29)-dien-28-oyl)imidazole], compared with BA itself and at concentrations that were active in vitro. These results suggest that BA is a useful platform for drug development, and the enhanced potency and varied biological activities of CBA-Im make it a promising candidate for further chemoprevention or chemotherapeutic studies. [Mol Cancer Ther 2007;6(7):2113–9] |
| تدمد: | 1538-8514 1535-7163 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7af07d37feaa0f1ccb23a3658e072dc3Test https://doi.org/10.1158/1535-7163.mct-07-0180Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7af07d37feaa0f1ccb23a3658e072dc3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15388514 15357163 |
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