SYNTHESIS AND ANTITUMOR-ACTIVITY OF WATER-SOLUBLE 2-BENZYL-1,2-DIAMINOBUTANE-ALPHA-OXYCARBOXYLATOPLATINUM(II) COMPLEXES

Nine new water-soluble platinum(II) complexes were synthesized and characterized. Racemic (+/-)-2-benzyl-1,2-diaminobutane or the corresponding enantiomers (+)-2-benzyl-1,2-diaminobutane and (-)-2-benzyl-1,2-diaminobutane were used as nitrogen chelate ligands. The chloride leaving groups of the resulting N,N'-2-benzyl-1,2-diaminobutanedichloroplatinum(II) complexes were replaced by the anions of four alpha-hydroxycarboxylic acids to increase the water solubility. As alpha-hydroxycarboxylic acids, lactic acid, glycolic acid, mandelic acid and alpha-hydroxyisobutyric acid were used. For N,N'-2-benzyl-1,2-diaminobutane-O,O'-lactatoplatinum(II), the different geometrical and optical isomers were separated. The antitumor activity of the platinum(II) complexes was examined in vitro towards the MDA-MB 231 breast cancer cell line and in vivo towards the P 388 leukemia of the CD2F1 mouse. Contrary to the insoluble dichloro complexes, the alpha-oxycarboxylatoplatinum(II) complexes exhibited good water solubility associated with a high antitumor activity.