Synthesis, anticancer activity and toxicity of a water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane].(3-hydroxyl-cyclobutane-1,1-dicarboxylate)}

doi:10.1016/j.jinorgbio.2014.07.013

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

	Synthesis, anticancer activity and toxicity of a water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane].(3-hydroxyl-cyclobutane-1,1-dicarboxylate)}
	Liu, Weiping 1; Jiang, Jing 1; Xie, Chengying2 ; Hou, Shuqian 1; Quan, Haitian2 ; Ye, Qingsong 1; Lou, Liguang2
刊名	JOURNAL OF INORGANIC BIOCHEMISTRY
	2014-11
卷号	140 页码:126-130
关键词	Platinum complexes Anticancer activity Toxicity Heptaplatin Derivative
ISSN号	0162-0134
DOI	10.1016/j.jinorgbio.2014.07.013
文献子类	Article
英文摘要	A water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]center dot(3-hydroxyl-cyclobutane-1,1-dicarboxylate)} was synthesized. The anticancer activity and toxicity were evaluated by comparing its interaction with DNA, cytotoxicity against four human cancer cell lines, antitumor efficiency in human gastric carcinoma NCI-N87 xenografts in nude mice, and preliminary side-effects in rats to those of its 4R,5R-optical isomer which is under preclinical development. Both isomers induce condensation of DNA to the same extent and have similar cytotoxicity, but show different antitumor activity and toxicity, probably owing to the difference in respective pharmacokinetic profiles. 4S,5S-Isomer seems to exhibit superior antitumor activity and less toxicity than 4R,5R-optical isomer as well as the parent heptaplatin. These results imply that 4S,5S-configuration as a new drug candidate may be better than 4R,5R-counterpart. (C) 2014 Elsevier Inc. All rights reserved.
资助项目	Natural Science Foundation of China[21161010] ; National Key R&D Program of China[2012BAE06B08] ; National Key R&D Program of China[2009ZX09103-109]
WOS关键词	ANTITUMOR-ACTIVITY ; PLATINUM COMPLEXES ; IN-VITRO ; CISPLATIN ; DESIGN ; AGENTS ; DRUGS ; CANCER ; DICHLOROACETATE ; CYTOTOXICITY
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000342608900016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276861]
专题	药理学第一研究室
通讯作者	Lou, Liguang
作者单位	1.Kunming Inst Precious Met, State Key Lab Platinum Grp Met, Kunming 650106, Yunnan, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Liu, Weiping,Jiang, Jing,Xie, Chengying,et al. Synthesis, anticancer activity and toxicity of a water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane].(3-hydroxyl-cyclobutane-1,1-dicarboxylate)}[J]. JOURNAL OF INORGANIC BIOCHEMISTRY,2014,140:126-130.
APA	Liu, Weiping.,Jiang, Jing.,Xie, Chengying.,Hou, Shuqian.,Quan, Haitian.,...&Lou, Liguang.(2014).Synthesis, anticancer activity and toxicity of a water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane].(3-hydroxyl-cyclobutane-1,1-dicarboxylate)}.JOURNAL OF INORGANIC BIOCHEMISTRY,140,126-130.
MLA	Liu, Weiping,et al."Synthesis, anticancer activity and toxicity of a water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane].(3-hydroxyl-cyclobutane-1,1-dicarboxylate)}".JOURNAL OF INORGANIC BIOCHEMISTRY 140(2014):126-130.