title: Potent anticancer activity and possible low toxicity of platinum(II) complexes with functionalized 1,1-cyclobutanedicarboxylate as a leaving ligand.
abstract: Two platinum(II) complexes, DN603 and DN604, were designed and prepared by using 3-oxocyclobutane-1,1-dicarboxylate as a ligand. The compounds were prepared according to the concept that incorporation of a functionalized moiety in the leaving ligand that did not affect its coordination bonding to the metal atom would play a key role in the anticancer activity of the resulting platinum complex. The newly prepared compounds were found to show potent in vitro anticancer activity comparable to cisplatin and oxaliplatin; especially DN604, which exhibited low acute toxicity similar to carboplatin, and presented acceptable solubility and stability in water. Chemical and biological results indicated that the functionalized moiety, uncoordinated, led to potent anticancer activity and low apparent toxicity of the platinum complexes by affecting the kinetic properties of the compounds.
authors.affiliation: Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189 (P.R. China), Fax: (+86) 83272381.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
authors.forename: Fengfan
authors.initials: F
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003503:Cyclobutanes / Q000737:chemistry* / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003503:Cyclobutanes; D003998:Dicarboxylic Acids; D008024:Ligands; D009944:Organoplatinum Compounds
keywords: antitumor agents; drug design; drug discovery; kinetics; platinum