Effects of 4-nitrobenzofurazans and their N-oxides on synthesis of protein and nucleic acid by murine leukemia cells.
A series of benzo-2,1,3-oxadiazoles (benzofurazans) and their N-oxides (benzofuroxans) inhibit incorporation of precursors into nucleic acids and protein by murine leukemia cells. At slighly higher levels, substantial single- and double-strand DNA breakage was observed. At still higher concentrations, inhibition of phosphorylation of uridine and thymidine was found. Structure-activity relationships show that only compounds bearing appropriate substitutions at positions 4 and 7 were effective inhibitors of biosynthetic pathways. Such compounds appear to interact with a wide variety of biological systems and may be useful in elucidating modes of macromolecule synthesis.
D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology*; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D007939:Leukemia L1210 / Q000378:metabolism; D007942:Leukemia, Experimental / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009574:Nitro Compounds / Q000494:pharmacology; D010069:Oxadiazoles; D010710:Phosphates / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
D001583:Benzoxazoles; D003497:Cyclic N-Oxides; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009574:Nitro Compounds; D010069:Oxadiazoles; D010710:Phosphates; D012334:RNA, Neoplasm; C011514:4-nitrobenzofurazan; C020160:benzofurazan; C014354:benzofuroxan; D013936:Thymidine; D014529:Uridine