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Coordination modes vs. antitumor activity: Synthesis and antitumor activity of novel platinum(II) complexes of N-substituted amino dicarboxylic acids

Title
Coordination modes vs. antitumor activity: Synthesis and antitumor activity of novel platinum(II) complexes of N-substituted amino dicarboxylic acids
Authors
Kim Y.-S.Song R.Chung H.C.Jun M.J.Sohn Y.S.
Ewha Authors
손연수
SCOPUS Author ID
손연수scopus
Issue Date
2004
Journal Title
Journal of Inorganic Biochemistry
ISSN
0162-0134JCR Link
Citation
vol. 98, no. 1, pp. 98 - 104
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The trans-(±)-1,2-diaminocyclohexaneplatinum(II) complexes of multidentate L-glutamate (Glu) and L-aspartate (Asp) were prepared and their antitumor activity was examined in relation with their coordination modes. All these complexes were obtained as a mixture of (O,O′)- and (O,N)-chelate isomers due to rapid isomerization of the initially formed (O,O′)-isomer to the thermodynamically more stable (O,N)-isomer. The (O,O′)/(O,N)- isomeric mixture with the mole ratio of 80/20 exhibited excellent antitumor activity while the pure (O,N)-isomer was only marginally active. Therefore, in order to prevent the linkage isomerization of the active (O,O′)-isomer to the inactive (O,N)-isomer, we have designed N-substituted amino dicarboxylic acids as a leaving group and prepared a new series of complexes, [Pt(dach)(RGlu)] and [Pt(dach)(RAsp)] (dach=trans-(±)-1,2- diaminocyclohexane; R=acetyl (Ac), propionyl (Pro), pivaloyl (Piv), carbobenzyloxy (Cbz) or phthaloyl (Phth)) and characterized by means of elemental analyses, and 1H NMR, 195Pt NMR and IR spectroscopies. The N-substituted amino dicarboxylate ligands were found to coordinate to platinum(II) ion through only the (O,O′)-chelation mode, and their Pt(II) complexes were chemically stable in aqueous solution. The present Pt(II) complexes of N-substituted amino dicarboxylic acids showed excellent antitumor activity against both murine leukemia L1210 and human tumor cells. Especially, the highly hydrophobic N-phthaloylglutamate complex, [Pt(dach)(PhthGlu)], exhibited an outstanding in vitro activity (IC 50=2.22 μM) on the human stomach cancer cells which are not responsive to cisplatin and carboplatin. © 2003 Elsevier Inc. All rights reserved.
DOI
10.1016/j.jinorgbio.2003.09.004
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자연과학대학 > 화학·나노과학전공 > Journal papers
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