Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways
| العنوان: | Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways |
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| المؤلفون: | Jiale Wu, Jicheng Liu, Jiafeng Wang, Haijun Wang, Yinglong Han, Yu Lin, Jing Wang, Jie Zhang, Ming Bu |
| المصدر: | Molecules Volume 26 Issue 21 Molecules, Vol 26, Iss 6356, p 6356 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Pharmaceutical Science, Organic chemistry, Antineoplastic Agents, Chemistry Techniques, Synthetic, Article, Analytical Chemistry, chemistry.chemical_compound, thiosemicarbazone, QD241-441, Downregulation and upregulation, Cell Line, Tumor, Drug Discovery, Humans, Physical and Theoretical Chemistry, Cytotoxicity, Semicarbazone, Cell Proliferation, antitumor, Membrane Potential, Mitochondrial, Semicarbazones, Betulin, betulin derivatives, semicarbazone, Molecular Structure, biology, Cytochrome c, apoptosis, Flow Cytometry, Molecular biology, Triterpenes, In vitro, Mitochondria, chemistry, Chemistry (miscellaneous), Apoptosis, Drug Design, biology.protein, Molecular Medicine, Reactive Oxygen Species, Biomarkers, Metabolic Networks and Pathways, Intracellular |
| الوصف: | Two new series of betulin derivatives with semicarbazone (7a–g) or thiosemicarbazone (8a–g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, 8f displayed the most potent cytotoxicity with an IC50 value of 5.86 ± 0.61 μM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound 8f could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression the downregulation of Bcl-2 expression activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9 and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound 8f may be used as a valuable skeleton structure for developing novel antitumor agents. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1420-3049 |
| DOI: | 10.3390/molecules26216356 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d926115a7ef83780598cc8fbdc0be8fcTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d926115a7ef83780598cc8fbdc0be8fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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| DOI: | 10.3390/molecules26216356 |