Platinum(II) and palladium(II) complexes with 2-acetyl pyridine and pyridine-2-carbaidehyde N(4)-ethyl-thiosemicarbazones, HAc4Et and HFo4Et respectively were synthesized and found to exhibit a cytotoxic potency in a very low micromolar range and to be able to overcome the cisplatin resistance of A2780/Cp8 cells. The biologically active complexes Pd(Fo4Et)(2) (1), Pd(Ac4Et)(2) (2), Pt(Fo4Et)(2) (3) and Pt(Ac4Et)(2) (4) were tested for their perturbation in model membrane bilayers. The aim was to investigate if there is a possible relation between their mechanism of action in membranes with their biological activity. Indeed, it was found that complexes of deprotonated HAc4Et, (2) and (4), are more perturbing than complexes of deprotonated HFo4Et, (1) and (3). (C) 2004 Elsevier B.V. All rights reserved.