Synthesis and antitumor activity of platinum complexes of protonated diamines

Abstract

Complexes of the formula cis-[Pt(H N + ∼N)(L)Cl 2], where (H N + ∼N) are the protonated diamines including 3-aminoquinuclidine, N-aminopiperidine, piperazine, N-methylpiperazine, 1,1,4-trimethylpiperazine, and N-methyl-1,4-diazabicyclo [2,2,2] octane (N-methyl-dabco) and L = SCN −, NO 2 −, Br −, and F −, were synthesized from the protonated diamine complexes, [Pt(H N + ∼N)Cl 3]. The antitumor activities of the complexes were evaluated in vitro against L1210 murine leukemia cells, and ID 50 values for the L-substituted complexes were compared to values of the parent complexes. In each case it was found that replacement of a chloride ion by SCN −, NO 2 −, Br −, or F −, either reduced or completely eliminated antitumor activity. This effect is explained in terms of the trans-directing ability of the ligand, L, compared to chloride. The NO 2-substituted complex of 3- aminoquinuclidine was tested in vivo and found to exhibit little or no antitumor activity.