A series of derivatives belonging to a new class of compounds (R-4-todit) were 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) derivative (IC50 = 0.06-5.1 mu M); T leukaemia and melanoma cells were the most susceptible cells to this inhibitor (IC50 0.06 mu M and 0.1 mu M, respectively). The effect of butyl(4)-todit was irreversible, and led to progressive cell death. The compound showed a comparable potency against exponentially growing and stationary phase cells, and against cell lines expressing the 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.
Antitumor activity of 4,5,6,7-tetrathiocino (1,2-b:3,4-b’) diimidazolyl - 1,3,8,10-tetrasubstituted - 2,9-dithiones (R4-todit)
PANI, ALESSANDRA;DEPLANO, PAOLA;
1998-01-01
Abstract
A series of derivatives belonging to a new class of compounds (R-4-todit) were 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) derivative (IC50 = 0.06-5.1 mu M); T leukaemia and melanoma cells were the most susceptible cells to this inhibitor (IC50 0.06 mu M and 0.1 mu M, respectively). The effect of butyl(4)-todit was irreversible, and led to progressive cell death. The compound showed a comparable potency against exponentially growing and stationary phase cells, and against cell lines expressing the 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.
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