Metal complexes as anticancer agents 2. Iron(III) and copper(II) bio-active complexes with N-6-benzylaminopurine derivatives

Iron(III) complexes with 2-(3-hydroxypropylamino)-6-benzylaniino-9-isopropy lpurine (Bohemin, HL1), in its protonized form, of the composition (H+HL1)( 2)[FeCl5]. 2H(2)O (1), (H+HL1)(2)[FeCl5]. 3H(2)O (2) have been prepared by two different routes. A new way for synthesis of copper(II) complex with 6- (2-chlorobenzylamino)purine (HL2), [Cu-2(mu -Cl)(2)(mu -HL2)(2)(HL2)(2)Cl-2 ]. 2H(2)O (3), together with the preparation of copper(II) complex with 6-( 3-chlorobenzylamino)purine (HL3), [Cu-2(mu -Cl)(2)(mu -HL3)(2)Cl-2] (4), is also reported. The characterization have been based on elemental analysis, electronic, infrared, ES + mass and Fe-57 Mossbauer spectra, conductivity data and magnetic susceptibility temperature measurements over the 4.5-300 K for 1-3, and 35-300 K for 4. temperature range, respectively. Molecular s tructure of an electroneutral form of the HL2 ligand, (HL2. 2H(2)O), and a protonized form of the HL3 ligand, (H+HL3-Cl), have been determined by a si ngle-crystal X-ray analysis. A mononuclear trigonal-bipyramidal (for 1 and 2), binuclear octahedral (for 3) and binuclear trigonal-bipyramidal (for 4) structures of the complexes were proposed mainly on the basis of spectral and magnetic properties. An S = 3/2-5/2 spin-admixed state in 1 and 2 was f ound to be related to the presence of [FeCl5](2-) (S = 3/2) and [FeCl5(H2O) ](2-) (S = 5/2) complex anions in I and 2, as found by Fe-57 Mossbauer spec troscopy. Cytotoxic activity of the complexes was determined by a calcein A M assay and IC50 values were also estimated. For testing, human malignant m elanoma cell line G-361. human osteogenic sarcoma cell line HOS, human chro nic myelogenous leukaemia K-562 and human breast adenocarcinoma cell line M CF7 were used. The inhibition of p34(cdc2) kinase by the complexes I and 2, which is known to be one of the important mechanisms responsible for cytot oxicity of cytokinin-derived compounds, was also studied. (C) 2001 Elsevier Science B.V. All rights reserved.