title: Synthesis and characterization of platinum(IV) anticancer drugs with functionalized aromatic carboxylate ligands: influence of the ligands on drug efficacies and uptake.
abstract: A series of trans-platinum(IV) complexes with functionalized aromatic carboxylate ligands, cis,cis,trans-Pt(NH3)2Cl2(CO2C6H4R)2 (R = H (3), p-vinyl (4), p-methoxy (5), p-iodo (6), p-cyano (7), or o-carboxyl (8)) was synthesized and characterized by spectroscopic methods. Crystal structures of 3, 4, 7, and 8 were obtained, which revealed that their structural conformations were influenced by intramolecular H-bonding interactions. The complexes were evaluated for cellular uptake and inhibition of cell proliferation against a panel of lung, colon, and breast carcinoma cell lines. The functionalization of the aromatic carboxylate ligand was found to have a profound influence on the uptake, and hence, efficacy, of this class of complex.
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, CH 1015 Lausanne, Switzerland.
authors.forename: Wee Han
authors.initials: WH
authors.lastname: Ang
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pilet
authors.forename: Rosario
authors.initials: R
authors.lastname: Scopelliti
authors.forename: François
authors.initials: F
authors.lastname: Bussy
authors.forename: Lucienne
authors.initials: L
authors.lastname: Juillerat-Jeanneret
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001565:Benzoates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D018360:Crystallography, X-Ray; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010795:Phthalic Acids / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001565:Benzoates; D002614:Chelating Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D010795:Phthalic Acids