Porphyrinogenic activity and ferrochelatase-inhibitory activity of sydnones in chick embryo liver cells.
3-[2-(2,4,6-Trimethylphenyl)thioethyl]-4-methylsydnone was shown to be a potent porphyrinogenic agent in chick embryo liver cells. The accumulation of protoporphyrin IX was consistent with the finding that ferrochelatase activity was inhibited. 3-Benzyl-4-phenylsydnone did not inhibit ferrochelatase activity and protoporphyrin IX was found to constitute only a minor fraction of the prophyrins. These results support the idea that the porphyrinogenicity of 3-[2-(2,4,6-trimethylphenyl)thioethyl]-4-methylsydnone is due to its catalytic activation by cytochrome P-450 leading to heme alkylation and formation of N-vinylprotoprophyrin IX which inhibits ferrochelatase.
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D003997:Dicarbethoxydihydrocollidine / Q000494:pharmacology; D005294:Ferrochelatase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008190:Lyases / Q000037:antagonists & inhibitors*; D010069:Oxadiazoles / Q000494:pharmacology*; D011166:Porphyrins / Q000096:biosynthesis*; D011524:Protoporphyrins / Q000096:biosynthesis; D013558:Sydnones / Q000494:pharmacology*
D010069:Oxadiazoles; D011166:Porphyrins; D011524:Protoporphyrins; D013558:Sydnones; C048192:3-(2-(2,4,6-trimethylphenyl)thioethyl)-4-methylsydnone; D003997:Dicarbethoxydihydrocollidine; D003577:Cytochrome P-450 Enzyme System; C028025:protoporphyrin IX; D008190:Lyases; D005294:Ferrochelatase