Evaluation of 1-(3,4-dichlorophenyl)-4-dimethylaminomethyl-1-nonen-3-one hydrochloride effect on nucleic acid and protein syntheses using murine leukemia L-1210 cells.
Several Mannich bases derived from conjugated styryl ketones were shown to have potent cytotoxicity toward murine leukemia L-1210 cells and Walker 256 carcinosarcoma cells in culture. The most cytotoxic derivative, (E)-1-(3,4-dichlorophenyl)-4-dimethylaminomethyl-1-nonen-3-one hydrochloride, profoundly inhibited the incorporation of tritiated leucine into protein(s) and tritiated deoxythymidine into DNA at concentrations of 0.79-1.32 muM in L-1210 cells. At higher concentrations, incorporation of triated uridine into RNA and tritiated deoxyuridine into DNA was inhibited to a lesser degree. This compound failed to inhibit the enzymes thymidylate synthetase or dihydrofolate reductase up to a concentration of 10-4 M and was ineffective in retarding the growth of the Walker 256 carcinosarcoma in rats.
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002279:Carcinoma 256, Walker / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D007939:Leukemia L1210 / Q000378:metabolism*; D008352:Mannich Bases / Q000494:pharmacology*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D013997:Time Factors
D000588:Amines; D004273:DNA, Neoplasm; D008352:Mannich Bases; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm