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  • Title: Platinum(II) complexes with N-monoalkyl 1R,2R-diaminocyclohexane derivatives as carrier ligands and 3-hydroxycyclobutane-1,1-dicarboxylate as a leaving group: potent cytotoxicity and DNA binding ability.
    Author: Fang L, Gou S, Zhao J, Sun Y, Cheng L.
    Journal: Eur J Med Chem; 2013 Nov; 69():842-7. PubMed ID: 24121235.
    Abstract:
    A series of novel platinum(II) complexes with N-monoalkyl 1R,2R-diaminocyclohexane derivatives and 3-hydroxycyclobutane-1,1-dicarboxylate as ligands were designed and synthesized. The cytotoxicity study revealed that most of synthesized complexes showed moderate to potent activity against all four tested tumor cell lines. Particularly, 1d showed much higher cytotoxic activity than carboplatin and oxaliplatin against MCF-7 and A549 cell lines. Due to the employment of N-monoalkyl 1R,2R-diaminocyclohexane derivatives and 3-hydroxycyclobutane-1,1-dicarboxylate as ligands, the calculated log P values of the complexes are around 1, suggesting a good balance of the lipophilicity and hydrophilicity. The aqueous solubility of 1d is also improved, reaches 24.6 mg/mL. Furthermore, both docking study and agarose gel electrophoresis have confirmed the DNA-binding ability of 1d.
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