Dimethylsilane polyamines, a new class of potential anticancer drugs

Several members of a new class of structural analogues of the natural polyamines which contain a S1(CH3)(2)- group in the central carbon chain have previously been found to be potent cytostatics to various tumor cell lines. These compounds have been tested with regard to their ability to inhibit the growth of Lewis lung carcinoma grafts in DBA/2 mice. All compounds exerted consistently antitumor effects, however,growth inhibition was only partial at one or two daily doses of 25 mu mol/kg of the drugs. Among the dimethylsilane tetramines only (6-amino-3-azahexyl),(7-amino-4-azaheptyl)-dimethylsilane (AzhexAzhepSi) reduced tumor growth to a significant degree. A major central nervous system pharmacologic effect of the compounds, hypothermia, limitates the administrable amount of the compounds. The dimethylsilane amines have polyamine antagonist properties, and are weak polyamine mimetics, as became obvious from their effect on tumor cells in culture and the present in vivo experiments.