Biochemical basis of cytotoxic activity of some new N'-oxides of N',N'-dimethylaminoalkylamides of dodecanoic acid.
The objective of the present investigation was to screen a series of new N'-oxides of N',N'-dimethylaminoalkylamides of dodecanoic acid for activity in vitro and to investigate the biochemical mode of action. On the basis of primary screening, one of the most active compounds, namely the N'-oxide of 10-(N',N'-dimethylaminodecyl)amide of dodecanoic acid (n = 10) was chosen for detailed biochemical study. This compound inhibited the incorporation of 14C-precursors (adenine, valine, thymidine, uridine) into appropriate macromolecules of P388 murine leukemia and Ehrlich ascites carcinoma cells. The amine oxide also interfered with energy-yielding processes (aerobic glycolysis, endogenous respiration). Cytotoxicity is a consequence of the cytolytic activity of the compounds mentioned above. Membranous effects were demonstrated by the measuring of the release of cytoplasmic materials absorbing at 260 and 280 nm, marker enzyme activities (LDH, MDH), release of protein from the cells into the culture medium, as well as by morphological examination. It is evident that the site of action of the amine oxides investigated was the biological membrane which, after interaction with the amine oxides, showed changes in molecular organization and osmotic and permeability characteristics.
Miko
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Department of Microbiology, Biochemistry and Biology, Slovak Technical University, Bratislava, Czechoslovakia.
Devínsky
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004734:Energy Metabolism / Q000187:drug effects; D007850:Lauric Acids / Q000494:pharmacology*; D051379:Mice; D009363:Neoplasm Proteins / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D012334:RNA, Neoplasm / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007850:Lauric Acids; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C030358:lauric acid