Design and Synthesis of Novel C14-Hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents

doi:10.1021/jm900342g

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	Design and Synthesis of Novel C14-Hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents
	Li, Zheng 2; Zhou, Zhao-Li 3; Miao, Ze-Hong 1; Lin, Li-Ping 1; Feng, Hui-Jin2 ; Tong, Lin-Jiang 1; Ding, Jian1,3 ; Li, Yuan-Chao 2
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2009-08-27
卷号	52 期号:16 页码:5115-5123
ISSN号	0022-2623
DOI	10.1021/jm900342g
文献子类	Article
英文摘要	It has long been considered that the free beta hydroxyl group at C14 of triptolide(1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) ora five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14 beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum ill vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of I and also produces a promising anticancer drug candidate with unique anticancer activities.
资助项目	Natural Science Foundation of China (NSFC)[30721005]
WOS关键词	TRIPTERYGIUM-WILFORDII ; MULTIDRUG-RESISTANCE ; CLINICAL-TRIALS ; CANCER-CELLS ; CHEMOTHERAPY ; APOPTOSIS ; DOXORUBICIN ; PATHWAY ; GROWTH ; TUMORS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000269042700014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279153]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室药物化学研究室
通讯作者	Ding, Jian
作者单位	1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China; 3.Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China
推荐引用方式 GB/T 7714	Li, Zheng,Zhou, Zhao-Li,Miao, Ze-Hong,et al. Design and Synthesis of Novel C14-Hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents[J]. JOURNAL OF MEDICINAL CHEMISTRY,2009,52(16):5115-5123.
APA	Li, Zheng.,Zhou, Zhao-Li.,Miao, Ze-Hong.,Lin, Li-Ping.,Feng, Hui-Jin.,...&Li, Yuan-Chao.(2009).Design and Synthesis of Novel C14-Hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents.JOURNAL OF MEDICINAL CHEMISTRY,52(16),5115-5123.
MLA	Li, Zheng,et al."Design and Synthesis of Novel C14-Hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents".JOURNAL OF MEDICINAL CHEMISTRY 52.16(2009):5115-5123.