Synthesis and characterization of platinum(IV) anticancer drugs with functionalized aromatic carboxylate ligands: influence of the ligands on drug efficacies and uptake.
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.
Ang
Wee Han
WH
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, CH 1015 Lausanne, Switzerland.
Pilet
Sébastien
S
Scopelliti
Rosario
R
Bussy
François
F
Juillerat-Jeanneret
Lucienne
L
Dyson
Paul J
PJ
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
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