Synthesis, characterization, cytotoxic activity, and cellular accumulation of dinuclear platinum complexes derived from N,N′-di-(2-aminoethyl)-1,3-diantino-2-propanol, aryl substituted N-benzyl-1,4-butanediamines, and N-benzyl-1,6-hexanediamines

This work describes the synthesis and characterization of six new dinuclear platinum complexes having N,N'-di-(2-aminoethyl)-1,3-diamino-2-propanol, aryl substituted N-benzyl-1,4-butanediamines and N-benzyl-1,6-hexanediamines as ligands. They were prepared by the reaction of cis-[PtCl2(DMSO)(2)] (DMSO=dimethyl sulfoxide) with the appropriate ligand in water, except for one of them, which was prepared from K2PtCl4. We also report the cytotoxic activity and cellular accumulation of three of these complexes in a human small-cell lung carcinoma cell line and its resistant subline. Resistant cells exhibited a lesser degree of cross-resistance to these compounds when compared to cisplatin. The accumulation of platinum in both cell lines followed the same pattern, i.e. approximately the same intracellular platinum concentration yielded the same cytotoxic effect independent of the nature of the platinum complex used. (C) 2003 Elsevier Science Inc. All rights reserved.