10-Boronic acid substituted camptothecin as prodrug of SN-38

doi:10.1016/j.ejmech.2016.03.063

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	10-Boronic acid substituted camptothecin as prodrug of SN-38
	Wang, Lei 1; Xie, Shao 2; Ma, Longjun 1; Chen, Yi2 ; Lu, Wei 1
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2016-06-30
卷号	116 页码:84-89
关键词	Boric acid Hydrogen peroxide Prodrug Camptothecin Antitumor
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2016.03.063
文献子类	Article
英文摘要	Malignant tumor cells have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential antitumor therapy. In this study, the 7-ethyl-10-boronic acid camptothecin (B1) was synthesized for the first time as prodrug of SN-38, by linking a cleavable aryl carbon-boron bond to the SN-38. Prodrug B1 selectively activated by H2O2, converted rapidly to the active form SN-38 under favorable oxidative conditions in cancer cells with elevated levels of H2O2. The cell survival assay showed that prodrug B1 was equally or more effective in inhibiting the growth of six different cancer cells, as compared to SN-38. Unexpectedly, prodrug B1 displayed even more potent Topo I inhibitory activity than SN-38, suggesting that it was not only a prodrug of SN-38 but also a typical Topo I inhibitor. Prodrug B1 also demonstrated a significant antitumor activity at 2.0 mg/kg in a xenograft model using human brain star glioblastoma cell lines U87MG. (C) 2016 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of China[81172936]
WOS关键词	VITRO ANTITUMOR-ACTIVITY ; POTENT CYTOTOXIC AGENTS ; HYDROGEN-PEROXIDE ; NATURAL-PRODUCTS ; CELL-MEMBRANE ; DERIVATIVES ; DESIGN ; CHEMISTRY ; CANCER ; SEMISYNTHESIS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000376803200009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275982]
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
通讯作者	Chen, Yi; Lu, Wei
作者单位	1.E China Normal Univ, Sch Chem & Mol Engn, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Lei,Xie, Shao,Ma, Longjun,et al. 10-Boronic acid substituted camptothecin as prodrug of SN-38[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2016,116:84-89.
APA	Wang, Lei,Xie, Shao,Ma, Longjun,Chen, Yi,&Lu, Wei.(2016).10-Boronic acid substituted camptothecin as prodrug of SN-38.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,116,84-89.
MLA	Wang, Lei,et al."10-Boronic acid substituted camptothecin as prodrug of SN-38".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 116(2016):84-89.