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

• Published in: European Journal of Inorganic Chemistry Vol. 2010; no. 22; pp. 3441 - 3448
• Main Authors: Dvořák, Lukáš, Popa, Igor, Štarha, Pavel, Trávníček, Zdeněk
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.08.2010; WILEY‐VCH Verlag; Wiley
• Subjects: Antitumor agents; Chemistry; Chemistry, Inorganic & Nuclear; Cytotoxicity; Nucleobases; Physical Sciences; Platinum; Science & Technology; Cytotoxicity; CRYSTAL-STRUCTURES; GENERAL STRATEGY; Nucleobases; LIBRARIES; NMR; Antitumor agents; SPECTROSCOPY; RESONANCE; Platinum; KINASE CDK INHIBITORS; CONSTRUCTION; CYTOKININS
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201000322

Six platinum(II) complexes of the general formula [Pt(cbdc)(HLn)2] (1–6; cbdc = cyclobutane‐1,1‐dicarboxylate and HL1–HL6 = benzyl‐substituted 6‐benzylamino‐2‐chloro‐9‐isopropylpurine derivatives) have been synthesized by the reaction of [Pt(cbdc)(dmso)2] with the corresponding HLn compound. 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 PtII 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 HLn molecules, that is, having a PtN2O2 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)(HL7)]·H2O (7a·H2O) intermediate [HL7 = 2‐chloro‐6‐(2‐methoxybenzyl)amino‐9‐isopropylpurine]. The geometry is slightly distorted square‐planar and the central PtII atom is coordinated to one bidentate cyclobutane‐1,1‐dicarboxylate dianion, one dmso molecule through the sulfur atom and one HL7 molecule through the N‐7 atom of the purine ring, that is, with a PtNO2S 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 IC50 (drug concentrations lethal for 50 % of the tumour cells) ranged from 4.5 to 14.1 μM for the K‐562 cells and from 4.3 to 21.0 μM 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. [Pt(cbdc)(HLn)2] complexes bearing the cyclobutane‐1,1‐dicarboxylate (cbdc) dianion and 6‐benzylamino‐2‐chloro‐9‐isopropylpurine derivatives (HLn) have been synthesized from [Pt(cbdc)(dmso)2], fully characterized and tested for their in vitro cytotoxicity against chronic myelogenous leukaemia and breast adenocarcinoma human cancer cell lines.