Antineoplastic and cytotoxic activity of beta-alkylamino-(para-substituted)propiophenone and beta-alkylamino-(6-methyl)-naphthone derivatives in murine and human tissue culture cells.

The beta-alkylamino(para-substituted)propiophenone and beta-alkylamino-(6-methyl)naphthone derivatives were evaluated for their antineoplastic effects in vitro in CF1 mice at 8 mg/kg/day intraperitoneal for 9 days. A number of these agents showed over 70% inhibition of Ehrlich ascites carcinoma growth. In in vitro cytotoxicity assays, these agents significantly inhibited the growth of a number of cancer cell lines from both human and murine origins. Some agents showed more activity than several standard anticancer drugs against certain cell lines. Three analogs, beta-(4-methyl)piperidino-(para-methyl)propiophenone (4), beta-piperidino-(para-ethoxy)propiophenone (13), and beta-hexamethyleneimino-(para-ethoxy)-propiophenone (14), were selected for mode of action studies and all showed significant inhibition of DNA and RNA syntheses at 100 microM after 60 min incubation. However, the most significant site of action was the inhibition of the activity of dihydrofolate reductase.