In vitro cytotoxicity and mode of action of 1-alkylpyrrolidine N-oxides.
A new class of nonaromatic amine oxides was synthesized and tested for cytotoxic activity in vitro. The aim of this study was to find if there is any correlation between the cytotoxic activity of the investigated 1-alkylpyrrolidine N-oxides and their structure (as a structural parameter the number of carbon atoms m in the alkyl chain was used). Maximum activity was achieved with 1-tetradecylpyrrolidine N-oxide (C14) which was chosen for further biochemical studies. Further lengthening led to decrease in activity. The drug inhibited the incorporation rate of [14C] precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of Ehrlich ascites cells, the extent of inhibition being dependent on both time and concentration of the compound in the incubation medium.
Miko
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M
Department of Microbiology, Biochemistry and Biology, Slovak Technical University, Bratislava.
Devinsky
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F
D000225:Adenine / Q000378:metabolism; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000378:metabolism; D014633:Valine / Q000378:metabolism
D009363:Neoplasm Proteins; D011759:Pyrrolidines; D012334:RNA, Neoplasm; D014633:Valine; D000225:Adenine; D013936:Thymidine; D014529:Uridine