期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 140, 期 -, 页码 126-130出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2014.07.013
关键词
Platinum complexes; Anticancer activity; Toxicity; Heptaplatin; Derivative
资金
- Natural Science Foundation of China [21161010]
- National Key R&D Program of China [2012BAE06B08, 2009ZX09103-109]
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.
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