Liu Xian-Xuan, Yang Yan-Ting, Wang Xiao, Wang Kai-Yi, Liu Jia-Qi, Lei Lei, Luo Xiao-Min, Zhai Rong, Fu Feng-Hua, Wang Hong-Bo, Bi Yi
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China.
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Eur J Med Chem. 2017 Dec 1;141:427-439. doi: 10.1016/j.ejmech.2017.09.016. Epub 2017 Oct 7.
In an attempt to arrive at a more potent cytotoxic agent than the parent compound α-hederagenin (H), 24 α-hederagenin derivatives (5-8, 11-24, 27-28, 31-32, and 35-36) were synthesized in a concise and efficient strategy and screened for in vitro cytotoxicity against the human cancer cell lines MKN45 and KB. Among these compounds, the polyamine derivative 15 exhibited more potency than the parent compound with IC values in the range of 4.22 μM-8.05 μM. Compound 15 increased Bax/bcl-2 ratio that disrupted the mitochondrial potential and induced apoptosis. Therefore, the present studies highlight the importance of polyamine derivatives of α-hederagenin in the discovery and development of novel anticancer agents.
为了获得一种比母体化合物α-常春藤皂苷元（H）更有效的细胞毒性剂，采用简洁高效的策略合成了24种α-常春藤皂苷元衍生物（5 - 8、11 - 24、27 - 28、31 - 32和35 - 36），并对其针对人癌细胞系MKN45和KB的体外细胞毒性进行了筛选。在这些化合物中，多胺衍生物15表现出比母体化合物更强的活性，其IC值在4.22 μM - 8.05 μM范围内。化合物15增加了Bax/bcl - 2比值，破坏了线粒体电位并诱导细胞凋亡。因此，本研究突出了α-常春藤皂苷元多胺衍生物在新型抗癌药物发现和开发中的重要性。
