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1. 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.

Author

Chopard C, Lenoir C, Rizzato S, Vidal M, Arpalahti J, Gabison L, Albinati A, Garbay C, and Kozelka J

Subjects
Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cell Line, Tumor, Cell Proliferation drug effects, Crystallography, X-Ray, Humans, Ligands, Organometallic Compounds chemistry, Salts chemistry, Diamines chemistry, Hydroxides chemistry, Organometallic Compounds chemical synthesis, Organometallic Compounds pharmacology, Platinum chemistry, Quaternary Ammonium Compounds chemistry
Abstract

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.

Published
2008
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