In Vitro CytotoxicActive PlatinumII Complexes Derived from Carboplatin and Involving Purine Derivatives

Autor: Dvoák, Lukáš, Popa, Igor, Štarha, Pavel, Trávníek, Zdenk
Zdroj: European Journal of Inorganic Chemistry; August 2010, Vol. 2010 Issue: 22 p3441-3448, 8p
Abstrakt: Six platinumII complexes of the general formula [PtcbdcHLn2] 1–6; cbdc = cyclobutane1,1dicarboxylate and HL1–HL6= benzylsubstituted 6benzylamino2chloro9isopropylpurine derivatives have been synthesized by the reaction of [Ptcbdcdmso2] with the corresponding HLncompound. The prepared complexes were characterized by elemental analysis and FTIR, Raman and NMR 1H, 13C, 15N and 195Pt spectroscopy. Based on the results of these techniques, it can be concluded that the central PtIIatom of the complexes 1–6is coordinated to two oxygen atoms originating from the cyclobutane1,1dicarboxylate group and to two nitrogen atoms from two HLnmolecules, that is, having a PtN2O2donor set. Detailed multinuclear and twodimensional NMR studies indicated the N7 atom to be the coordination site of the purine derivatives. The coordination mode was proven by a singlecrystal Xray analysis of the [PtcbdcdmsoHL7]·H2O 7a·H2O intermediate [HL7= 2chloro62methoxybenzylamino9isopropylpurine]. The geometry is slightly distorted squareplanar and the central PtIIatom is coordinated to one bidentate cyclobutane1,1dicarboxylate dianion, one dmso molecule through the sulfur atom and one HL7molecule through the N7 atom of the purine ring, that is, with a PtNO2S donor set. The complexes 1–6were tested for their in vitro cytotoxicity against K562 chronic myelogenous leukaemia and MCF7 breast adenocarcinoma human cancer cell lines. Values of IC50drug concentrations lethal for 50  of the tumour cells ranged from 4.5 to 14.1 μMfor the K562 cells and from 4.3 to 21.0 μMfor the MCF7 cells. The in vitro cytotoxicities were in several cases comparable or even higher than those of therapeutically used platinumbased anticancer drugs, that is, cisplatin, carboplatin andoxaliplatin.
Databáze: Supplemental Index