Synthesis and antitumour activity of platinum(II) and platinum(IV) complexes containing ethylenediamine-derived ligands having alcohol, carboxylic acid and acetate substituents - Crystal and molecular structure of [(PtLCl2)-Cl-4]center dot H2O where L-4 is ethylenediamine-N,N ‘-diacetate

Abstract

Several cisplatin analogues of ethylenediamine-derived ligands containing alcohol, carboxylic acid and acetate substituents have been prepared and characterised, Oxidation of some of these square planar platinum(II) complexes using aqueous hydrogen peroxide gave octahedral platinum(IV) complexes, containing trans hydroxo ligands. Acetylation of the hydroxo ligands was achieved by reaction with acetic anhydride, giving complexes which are analogues of the antitumour drug, JM-216. Oxidation of the complex [Pt(H2L4)Cl-2], where H2L4 is ethylenediamine-N,N’-diacetic acid, with H2O2 gave the platinum(IV) complex [(PtLCl2)-Cl-4].H2O in which L-4 is tetradentate as shown by a crystal and molecular structure. This complex was previously reported to be [Pt(HL4)(OH)Cl-2] in which HL4 is tridentate. Several of the complexes were tested for antitumour activity against five human ovarian carcinoma cell lines. IC50 values range from 4.0 muM for cis,trans-PtCl2(OH)(2)(NH2CH2CH2NHCH2CH2OH) against the CH1 cell line to >25 muM indicating moderate to low activity relative to other platinum complexes. (C) 2001 Elsevier Science B.V. All rights reserved.