Antineoplastic activities of 2,3,4-chloro-substituted beta-alkylaminopropiophenone derivatives in CF1 mice and in murine and human tumor cells.
A series of beta-alkylaminopropiophenone derivatives were demonstrated to be potent antineoplastic agents. Several compounds showed activity against Ehrlich ascites carcinoma growth in CF1 mice by demonstrating over 70% inhibition. Most of these agents proved to be potent cytotoxic agents in inhibiting the growth of a number of murine and human cancer cell lines grown in tissue culture. Their ED50 values were comparable to those of the selected standard anticancer drugs, such as 6-MP, ara-C, hydroxyurea, 5-FU, 6-aza-UMP, etoposide, antimycin A, actinomycin D and cycloheximide. In the mode of action studies in Tmolt3 cells, beta-(3",5"-dimethyl)piperidinopropiophenone was observed to reduce DNA and RNA synthesis significantly at 25 microM within 60 min incubation. The site of action of this agent appears to involve the reduction of the activities of Tmolt3 DNA polymerase alpha 1 dihydrofolate reductase, PRPP-amido transferase and ribonucleoside reductase.
Huang
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Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Hall
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D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D011427:Propiophenones / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011427:Propiophenones