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.
van Zutphen
Steven
S
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300, RA Leiden, The Netherlands.
Pantoja
Elena
E
Soriano
Rosario
R
Soro
Carlos
C
Tooke
Duncan M
DM
Spek
Anthony L
AL
den Dulk
Hans
H
Brouwer
Jaap
J
Reedijk
Jan
J
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