In Vitro Cytotoxic‐Active Platinum(II) Complexes Derived from Carboplatin and Involving Purine Derivatives

Abstract

Abstract Six platinum(II) complexes of the general formula [Pt(cbdc)(HL n ) 2 ] ( 1 – 6 ; cbdc = cyclobutane‐1,1‐dicarboxylate and HL 1 –HL 6 = benzyl‐substituted 6‐benzylamino‐2‐chloro‐9‐isopropylpurine derivatives) have been synthesized by the reaction of [Pt(cbdc)(dmso) 2 ] with the corresponding HL n compound. The prepared complexes were characterized by elemental analysis and FTIR, Raman and NMR ( 1 H, 13 C, 15 N and 195 Pt) spectroscopy. Based on the results of these techniques, it can be concluded that the central Pt II atom of the complexes 1 – 6 is coordinated to two oxygen atoms originating from the cyclobutane‐1,1‐dicarboxylate group and to two nitrogen atoms from two HL n molecules, that is, having a PtN 2 O 2 donor set. Detailed multinuclear and two‐dimensional NMR studies indicated the N‐7 atom to be the coordination site of the purine derivatives. The coordination mode was proven by a single‐crystal X‐ray analysis of the [Pt(cbdc)(dmso)(HL 7 )] · H 2 O ( 7a· H 2 O) intermediate [HL 7 = 2‐chloro‐6‐(2‐methoxybenzyl)amino‐9‐isopropylpurine]. The geometry is slightly distorted square‐planar and the central Pt II atom is coordinated to one bidentate cyclobutane‐1,1‐dicarboxylate dianion, one dmso molecule through the sulfur atom and one HL 7 molecule through the N‐7 atom of the purine ring, that is, with a PtNO 2 S donor set. The complexes 1 – 6 were tested for their in vitro cytotoxicity against K‐562 (chronic myelogenous leukaemia) and MCF7 (breast adenocarcinoma) human cancer cell lines. Values of IC 50 (drug concentrations lethal for 50 % of the tumour cells) ranged from 4.5 to 14.1 μ M for the K‐562 cells and from 4.3 to 21.0 μ M for the MCF7 cells. The in vitro cytotoxicities were in several cases comparable or even higher than those of therapeutically used platinum‐based anticancer drugs, that is, cisplatin, carboplatin andoxaliplatin.