Antitumor activity of 4,5,6,7-tetrathiocino(1,2-b : 3,4-b ')diimidazolyl-1,3,8,10-tetrasubstituted-2,9-dithiones (R-4-todit)

A series of derivatives belonging to a new class of compounds (R-4-todit) w ere highly cytotoxic to a panel of leukaemia- and solid tumour-derived cell lines (IC50 = 0.06-20 mu M). The most potent compound was the butyl(4) der ivative (IC50 = 0.06-5.1 mu M); T leukaemia and melanoma cells were the mos t susceptible cells to this inhibitor (IC50 0.06 mu M and 0.1 mu M, respect ively). The effect of butyl(4)-todit was irreversible, and led to progressi ve cell death. The compound showed a comparable potency against exponential ly growing and stationary phase cells, and against cell lines expressing th e MDR phenotype. The cytotoxicity of butyl(4)-todit in human normal PBL was up to 20 fold lower than that shown against T leukaemia cells. When tested for antiangiogenic activity in vivo, 1.5 mg/Kg butyl(4)-todit resulted in over 70%, inhibition of the angiogenesis process induced in mice by Kaposi' s sarcoma cell secreted products.