title: 4-Halovinyl- and 4-ethynyl-4-deformylpyridoxal derivatives and related analogues as potentially irreversible antagonists of vitamin B6.
abstract: Analogues of pyridoxal bearing alpha- and beta-chlorovinyl, beta-bromovinyl, butadienyl, acetyl, and 1-butenyl groups in place of the formyl group have been synthesized by subjecting 3,alpha5-di-O-benzylpyridoxal to appropriate Wittig or Grignard reactions. Similar methods yielded one-carbon homologues of pyridoxal and pyridoxol. Synthesis of the 4-ethynyl analogue of pyridoxal was achieved by dehalogenating blocked beta-halovinyl derivatives. The substituted vinyl and the ethynyl analogues were found to be active as inhibitors of mouse mammary adenocarcinoma cells grown in cell culture at an ID50 of 10(-5)-10(-6) M. The inhibitory activity of the 4-ethynyl analogue could be partially reversed by pyridoxal. This analogue was found to inhibit pyridoxal phosphokinase, and its 5'-phosphate was likewise found to be a potent noncompetitive inhibitor of pyridoxine-P oxidase.
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D002478:Cells, Cultured; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011736:Pyridoxine / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011730:Pyridoxal; D010088:Oxidoreductases; D011736:Pyridoxine