New antitumour active platinum compounds containing carboxylate ligands in trans geometry: synthesis, crystal structure and biological activity.
New asymmetric trans-platinum(II) complexes, composed of an isopropylamine, an azole and two carboxylate leaving groups, are presented. The crystal and molecular structures of one of the complexes has been determined and the cytotoxicity and reactivity with 5'-guanosine monophosphate is reported. The complexes show a reduced reactivity, but no decrease in cytotoxic activity compared to their chloro-counterparts. Furthermore the complexes largely overcome cisplatin resistance, they therefore present an interesting class of antitumour active trans-platinum complexes.
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300, RA Leiden, The Netherlands.
Steven
S
van Zutphen
Elena
E
Pantoja
Rosario
R
Soriano
Carlos
C
Soro
Duncan M
DM
Tooke
Anthony L
AL
Spek
Hans
H
den Dulk
Jaap
J
Brouwer
Jan
J
Reedijk
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy*; D017671:Platinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D008024:Ligands; D017671:Platinum Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue