Antitumor Action of Dichloro (4,5–dimethyl–o–phenylenediamine–N,N') platinum (II) 1

Summary

Dichloro (4,5–dimethyl–o–phenyl–enediamine–N,N′)platinum (II) (DDPP) was synthesized by the reaction of 4,5–dimethyl–o–phenylenediamine with potassium tetrachlo–roplatinate. The resulting compound extended up to 176% the survival times of BALB/c mice bearing the Ehrlich ascites tumor and up to 74% the survival times of BDF₁ mice bearing the L1210 leukemia. In studies using Ehrlich ascites tumor cells in vitro, DDPP was found to be a potent inhibitor of synthesis of DNA, RNA, and protein; the concentrations which conferred 50% inhibition following 1.5 hr of incubation with the compound were 3 × 10-⁵ to 5 × 10-⁵ M. Inhibition of nucleic acid and protein synthesis in vitro, once established, was not ameliorated by washing the cells with fresh medium devoid of DDPP. Cellular DNA, RNA, and protein, each appropriately labeled with a radioisotopically labeled precursor, became more acid–soluble upon incubation of the cells in vitro with DDPP. The rate of loss of viability of cells incubated in vitro with DDPP, as assessed by the trypan blue exclusion method, was found to be considerably greater than the rate obtained upon incubation of cells with an equivalent concentration of cis–dichlorodiammineplatinum(II).