Design, synthesis and biological evaluation of novel homocamptothecin analogues as potent antitumor agents

doi:10.1016/j.bmc.2015.03.031

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

	Design, synthesis and biological evaluation of novel homocamptothecin analogues as potent antitumor agents
	Wang, Lei 1; Xie, Shao 2; Ma, Longjun 1; Chen, Yi2 ; Lu, Wei 1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2015-05-01
卷号	23 期号:9 页码:1950-1962
关键词	Homocamptothecin Lactone stability Water solubility Anticancer drug
ISSN号	0968-0896
DOI	10.1016/j.bmc.2015.03.031
文献子类	Article
英文摘要	Fifteen novel homocamptothecin derivatives with alpha-OMe substituted E-rings were designed and synthesized. All of the derivatives exhibited similar or superior cytotoxicities compared with that of SN-38, and they inhibited Topo I activity in a cell-free assay in a manner similar to that of SN-38, confirming that they represent a new class of Topo I inhibitors. Notably, the water soluble compound 36o (1.2 mg/mL) exhibited increased lactone stability, and at 0.5 mg/kg and 3.0 mg/kg, it demonstrated significant antitumor activity in mice bearing a xenograft model using human colon cancer cell line HT-29. On the basis of these positive results, further development of 36o-related compounds as potential anticancer clinical trial candidates is definitely warranted. (C) 2015 Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[81172936]
WOS关键词	RING-MODIFIED CAMPTOTHECIN ; TOPOISOMERASE-I ; LACTONE RING ; CHEMICAL-MODIFICATION ; INHIBITORY-ACTIVITIES ; LUOTONIN-A ; DERIVATIVES ; 7-ETHYLCAMPTOTHECIN ; 20(S)-CAMPTOTHECIN ; NSC-100880
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000352698700005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276558]
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
作者单位	1.E China Normal Univ, Sch Chem & Mol Engn, 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. Design, synthesis and biological evaluation of novel homocamptothecin analogues as potent antitumor agents[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2015,23(9):1950-1962.
APA	Wang, Lei,Xie, Shao,Ma, Longjun,Chen, Yi,&Lu, Wei.(2015).Design, synthesis and biological evaluation of novel homocamptothecin analogues as potent antitumor agents.BIOORGANIC & MEDICINAL CHEMISTRY,23(9),1950-1962.
MLA	Wang, Lei,et al."Design, synthesis and biological evaluation of novel homocamptothecin analogues as potent antitumor agents".BIOORGANIC & MEDICINAL CHEMISTRY 23.9(2015):1950-1962.