Antineoplastic activities of alpha-methyl-beta-alkylaminopropiophenone derivatives in tissue culture cells.

A series of a-methyl-beta-alkylaminopropiophenone derivatives demonstrated potent antineoplastic effects. In CF1 mice, three compounds showed over 70% inhibition against the Ehrlich ascites carcinoma growth. In tissue culture cells, most of these agents demonstrated potent cytotoxicity in suppressing the growth of a number of murine and human cancer cell lines. In the mode of action studies in Tmolt-3 cells, alpha-methyl-beta-hexamethyleneiminopropiophenone (#14) was observed to reduce DNA synthesis significantly at 25 microM within 60 minutes incubation. The site of action of this agent appears to involve the reduction of purine de novo synthesis and IMP dehydrogenase activity. But significant inhibition of dihydrofolate reductase activity and DNA strand scission was noted.