Relations between structure and antitumor activity of cis-dichloro[bis(oligopeptide ester)platinum(II)] complexes

Abstract

Several title compds., cis- and trans-[PtA2X2] complexes (A = esters of oligopeptides; X = Cl, oxalate, or malonate), were tested for their ability to inhibit thymidine 3H incorporation by suspensions by ADJ/PC6 plasmacytoma cells, as an index of antitumor action. The effect was markedly dependent on the type, no., and sequence of the amino acids in the peptide component. The most active compd. was cis-[Pt(Gly-GlyOEt)2Cl2] [60426-60-0], whose activity was comparable with that of mitomycin C, amethopterin, or 5-fluorouracil. The isomeric trans-[Pt(Gly-GlyOEt)2Cl2] [39680-31-4] had insignificant activity. Substitution of other amino acids for the glycyl residue directly coordinated to the Pt markedly decreased antitumor activity, as did replacement of Gly-GlyOEt by Gly-Gly-GlyOEt. There was a close correlation between the ability of the compds. to inhibit thymidine uptake in the above system and their inhibition of ADJ/PC6 plasmacytoma growth in mice. Brief data are also given on the UV difference spectra of DNA after interaction with some of the Pt compds.