- 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)}
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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)} 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.
- Liu, Weiping,Jiang, Jing,Xie, Chengying,Hou, Shuqian,Quan, Haitian,Ye, Qingsong,Lou, Liguang
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- Platinum(II) complex and processes for preparing the same
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Disclosed herein are novel platinum(II) complexes having a potent anti-tumor activity which are represented by the formula (1), STR1 wherein R1 and R2, which may be the same or different, are a hydrogen atom or a C1-4 alkyl group, respectively, or jointly form a cycloalkane group together with the carbon atom attached thereto; two Xs jointly form a group represented by formula (a) or (b) wherein, R3 is a hydrogen atom or a methyl group; R4 and R5, which may be the same or different, are a hydrogen atom or a C1-4 alkyl group, respectively, or jointly form a cyclobutane together with the carbon thereto; and the absolute configurations at the respective chiral centers in the 4,5-bis(aminomethyl)-1,3-dioxolane moiety are (4R,5R) or (4S,5S); processes for the preparing the same; and their use for treating animal or human cancer. Further, disclosed herein are novel intermediates useful for the preparation of the platinum(II) complexes and processes for preparing said intermediates.
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- Synthesis and antitumor activity of a series of [2-substituted-4,5- bis(aminomethyl)-1,3-dioxolane]platinum(II) complexes
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The synthesis, physical properties, antitumor activity, structure-activity relationships, and nephrotoxicity of a series of [2-substituted-4,5- bis(aminomethyl)-1,3-dioxolane]platinum(II) complexes are described. The 42 platinum(II) complexes having a sev
- Kim,Kim,Gam,Cho,Kim,Tai,Kim,Hong -,Park
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p. 1471 - 1485
(2007/10/02)
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