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.
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.
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Southeast University, Nanjing 211189, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003503:Cyclobutanes / Q000737:chemistry*; D003514:Cyclohexylamines / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry*; D003998:Dicarboxylic Acids / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003503:Cyclobutanes; D003514:Cyclohexylamines; D003959:Diamines; D003998:Dicarboxylic Acids; D008024:Ligands; D009944:Organoplatinum Compounds; D004247:DNA
keywords: 1R,2R-Diaminocyclohexane; 3-Hydroxycyclobutane-1,1-dicarboxylic acid; Cytotoxicity; Platinum(II) complex