DNA binding andin vitro antileukemic activity of dimeric and tetrameric platinated complexes derived fromp-isopropylbenzaldehyde thiosemicarbazone

Abstract

p-Isopropylbenzaldehyde thiosemicarbazone (p-is.TSCN) (1) reacts with [Pt(µ-Cl)(η3-C4H7)]2 to form a dinuclear [Pt(µ-Cl)(p-is.TSCN)]2 complex (2) and a cyclometallated cluster [Pt(p-is.TSCN)]4 (3). Biological testing of these complexes against HL-60 and U-937 human leukemic cells suggest that complexes 2 and 3 may be endowed with important cytotoxic activity properties since they exhibit IC50 values (50% inhibition of cell growth) in the micromolar range, as does the clinically used drug cisplatin (cis-DDP). Analysis of the interaction of compounds 2 and 3 with DNA indicates that the kinetics of DNA platination due to compounds 2 and 3 is faster than that of cisplatin and that after 24 h of incubation most of the platinum centers are bound to DNA. Thus, it is likely that the cytotoxic activity displayed by compounds 2 and 3 may be correlated with their high level of DNA platination. Copyright © 1998 John Wiley & Sons, Ltd.