In vitro cytotoxic activity of 1-alkylpiperidine N-oxides and quantitative structure-activity relationships.
The main objective of the present investigation was to screen a series of 1-alkylpiperidine N-oxides for in vitro cytotoxicity, and to find out whether there is a quantitative structure-activity correlation (QSAR) between cytotoxic effect represented here by inhibition of incorporation of [14C]adenine into nucleic acid or [14C]valine into proteins in Ehrlich ascites carcinoma (EAC) cells and structure (as a structural parameter the number of carbon atoms m in the alkyl chain was used). On the basis of primary screening, one of the most active compounds, i.e. 1-decylpiperidine N-oxide, was chosen for further biochemical study. The drug inhibited the incorporation rate of 14C-labeled precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of Ehrlich cells, the extent of inhibition being dependent on both time and concentration of the compound in the incubation medium. The lengthening of the alkyl chain in 1-alkylpiperidine N-oxides positively affected their cytotoxic activity in Ehrlich cells. For these compounds the optimal m value is 12-15.
Miko
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M
Department of Microbiology, Biochemistry and Biology, Slovak Technical University, Bratislava.
Devinsky
F
F
D000225:Adenine / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002250:Carbon Radioisotopes; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology* / Q000633:toxicity; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D046911:Macromolecular Substances; D010880:Piperidines / Q000494:pharmacology* / Q000633:toxicity; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014633:Valine / Q000378:metabolism
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D003497:Cyclic N-Oxides; D004273:DNA, Neoplasm; D046911:Macromolecular Substances; D010880:Piperidines; D012334:RNA, Neoplasm; D014633:Valine; D000225:Adenine