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  • Title: Synthesis, cytotoxicity and DNA binding levels of tri-functional mononuclear platinum(II) complexes.
    Author: Zhang J, Gong Y, Zheng X, Yang M, Cui J.
    Journal: Eur J Med Chem; 2008 Feb; 43(2):441-7. PubMed ID: 17587465.
    Abstract:
    Seven new tri-functional mononuclear platinum(II) complexes (a-g) have been synthesized and characterized by elemental analysis, conductivity, thermal analysis, IR, UV and (1)H NMR spectral techniques. The cytotoxicity of these complexes was tested by MTT and SRB assays. The cell cycle analysis and the levels of total platinum bound to DNA were measured by flow cytometry and ICP-MS. The results indicate that the complexes (a-g) have selectivity against tested carcinoma cell lines; they have weaker cytotoxicity against HCT-8 and MCF-7. Complexes a, b, d and g also exert weaker cytotoxicity against BGC-823 and complexes a, b, e and f have better cytotoxicity against EJ, but their cytotoxicity is weaker than that of cisplatin. Complexes c, e and f, confer substantially greater cytotoxicity against HL-60 with an IC(50) value of 7.68+/-0.23, 3.87+/-0.19 and 2.41+/-0.18 microM, respectively, moreover, cytotoxicity of complex f is equal to that of cisplatin. Complexes c, e and f cause significant G(2)/M arrest and a concomitant decrease of cell population in G(1) and S phases. The total DNA-platination levels of them are higher than that of cisplatin under the same experimental conditions. It suggests that there is no correlation between total DNA-platination levels in HL-60 cells and cytotoxicity of complexes. When leaving groups are aromatic carboxylates, the complexes have better cytotoxicity, moreover, the substituent in benzene ring also influences cytotoxicity. In addition, when leaving groups are dicarboxylates, dicarboxylates coordinating with platinum through oxygen atoms form different chelate cycle and cycle size also affects their cytotoxicity.
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