Anti-tumor effect of dithiole compounds

A series of dithiole compounds, N-(1,3-dithiole-2-ylidene)-N,N-dialkyl-ammonium salts, was synthesized and tested for anti-tumor activity. Most of them exhibited a potent cytotoxic activity against cultured cells at IC50 concentrations less than 1 micrograms/ml. They were also effective in increasing the life-span of mice bearing L1210 leukemic cells. Their anti-tumor activities both in vitro and in vivo were related to the length of alkyl chain moieties, among which EX-015, having n-decyl chains, was found to be most effective in vivo; EX-015 prolonged the survival time of mice implanted with L1210 cells by 69% when given once daily for 5 days at 0.8 mg/kg. In addition, EX-015 inhibited the RNA and protein syntheses of L1210 cells, but less so with the DNA synthesis.