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Mitochondria-targeted betulinic and ursolic acid derivatives: synthesis and anticancer activity
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-09-13 00:00:00 , DOI: 10.1039/c7md00248c Darya A Nedopekina 1 , Rinat R Gubaidullin 1 , Victor N Odinokov 1 , Polina V Maximchik 2 , Boris Zhivotovsky 2, 3 , Yuriy P Bel'skii 4 , Veniamin A Khazanov 4 , Arina V Manuylova 4 , Vladimir Gogvadze 2, 3 , Anna Yu Spivak 1
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-09-13 00:00:00 , DOI: 10.1039/c7md00248c Darya A Nedopekina 1 , Rinat R Gubaidullin 1 , Victor N Odinokov 1 , Polina V Maximchik 2 , Boris Zhivotovsky 2, 3 , Yuriy P Bel'skii 4 , Veniamin A Khazanov 4 , Arina V Manuylova 4 , Vladimir Gogvadze 2, 3 , Anna Yu Spivak 1
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A series of new betulinic and ursolic acid conjugates with a lipophilic triphenylphosphonium cation, meant to enhance the bioavailability and mitochondriotropic action of natural triterpenes, have been synthesized. The in vitro experiments on three human cancer cell lines (MCF-7, HCT-116 and TET21N) revealed that all the obtained triphenylphosphonium triterpene acid derivatives not only showed higher cytotoxicity as compared to betulinic acid but were also markedly superior in triggering mitochondria-dependent apoptosis, as assessed using a range of apoptosis markers such as cytochrome c release, stimulation of caspase-3 activity, and cleavage of poly(ADP-ribose) polymerase, which is one of the targets of caspase 3. The IC50 was much lower for all triphenylphosphonium derivatives when compared to betulinic acid. Out of the tested group of conjugates, the most potent toxicity was exhibited by the betulinic acid conjugate 9 (for 9, the IC50 values against MCF-7 and TET21N cells were 0.70 μM and 0.74 μM; for betulinic acid (BA), IC50 > 25 μM against MCF-7 cells).
中文翻译：
线粒体靶向的桦木酸和熊果酸衍生物：合成和抗癌活性
合成了一系列新的桦木酸和熊果酸与亲脂性三苯基鏻阳离子的缀合物，旨在增强天然三萜的生物利用度和促线粒体作用。对三种人类癌细胞系（MCF-7、HCT-116和TET21N）的体外实验表明，所有获得的三苯基鏻三萜酸衍生物不仅表现出比桦木酸更高的细胞毒性，而且在触发线粒体依赖性方面也明显优于细胞凋亡，使用一系列细胞凋亡标记物进行评估，例如细胞色素c释放、caspase-3 活性刺激和聚 (ADP-核糖) 聚合酶（Caspase 3 的靶标之一）的裂解。IC 50低得多与桦木酸相比，所有三苯基鏻衍生物。在测试的缀合物组中，桦木酸缀合物9表现出最强的毒性（对于9 ，针对 MCF-7 和 TET21N 细胞的 IC 50值为 0.70 μM 和 0.74 μM；对于桦木酸 (BA)，IC 50 值为 0.70 μM 和 0.74 μM）。 50 > 25 μM 针对 MCF-7 细胞）。
更新日期：2017-09-13
中文翻译：
线粒体靶向的桦木酸和熊果酸衍生物：合成和抗癌活性
合成了一系列新的桦木酸和熊果酸与亲脂性三苯基鏻阳离子的缀合物，旨在增强天然三萜的生物利用度和促线粒体作用。对三种人类癌细胞系（MCF-7、HCT-116和TET21N）的体外实验表明，所有获得的三苯基鏻三萜酸衍生物不仅表现出比桦木酸更高的细胞毒性，而且在触发线粒体依赖性方面也明显优于细胞凋亡，使用一系列细胞凋亡标记物进行评估，例如细胞色素c释放、caspase-3 活性刺激和聚 (ADP-核糖) 聚合酶（Caspase 3 的靶标之一）的裂解。IC 50低得多与桦木酸相比，所有三苯基鏻衍生物。在测试的缀合物组中，桦木酸缀合物9表现出最强的毒性（对于9 ，针对 MCF-7 和 TET21N 细胞的 IC 50值为 0.70 μM 和 0.74 μM；对于桦木酸 (BA)，IC 50 值为 0.70 μM 和 0.74 μM）。 50 > 25 μM 针对 MCF-7 细胞）。
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