Synthetic route to dinuclear platinum(II) complexes [{trans-PtCl(NH3)2}2(mu-L)]2+ (L = aliphatic or heterocyclic diamine) as potential antitumor agents, exploiting the mutual activation of hydroxido ligands and ammonium groups.
A simple and efficient method for the synthesis of potentially antitumor-active dinuclear platinum complexes of the general formula [{trans-PtCl(NH3)2}2(mu-L)]((n+2)+) (L = aliphatic or heterocyclic diamine; n = charge of L) is presented. The procedure is based on the mutual in situ activation of trans-[PtCl(OH)(NH3)2] and the linker L in the form of a diammonium salt. This synthetic pathway yielded the Farrell compound [{trans-PtCl(NH3)2}2{mu-NH2(CH2)6NH2}]Cl2 (BBR3005) in quantitative yield. Using the same procedure, we prepared the new pyrazolate-bridged compound [{trans-PtCl(NH3)2}2(mu-pz)]Cl, determined its X-ray structure, and tested its cytotoxicity against three wild-type and one cisplatin-resistant cell lines.
Chopard
Claude
C
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601, CNRS, Université Paris Descartes, 45 rue des Saints-Pères, 75270 Paris, France.
Lenoir
Christine
C
Rizzato
Silvia
S
Vidal
Michel
M
Arpalahti
Jorma
J
Gabison
Laure
L
Albinati
Alberto
A
Garbay
Christiane
C
Kozelka
Jirí
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D003959:Diamines / Q000737:chemistry*; D006801:Humans; D006878:Hydroxides / Q000737:chemistry*; D008024:Ligands; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012492:Salts / Q000737:chemistry
D000970:Antineoplastic Agents; D003959:Diamines; D006878:Hydroxides; D008024:Ligands; D009942:Organometallic Compounds; D000644:Quaternary Ammonium Compounds; D012492:Salts; D010984:Platinum; C031356:hydroxide ion