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...

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Bibliographic Details
Published in:FEBS letters 1986-03, Vol.197 (1), p.17-20
Main Authors: Sutherland, E.P., Marks, G.S., Grab, L.A., de Montellano, P.R.Ortiz
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cells, Cultured
Chick Embryo
Cytochrome P-450 Enzyme System - physiology
Dicarbethoxydihydrocollidine - pharmacology
Ferrochelatase - antagonists & inhibitors
General pharmacology
Liver - drug effects
Liver - metabolism
Lyases - antagonists & inhibitors
Medical sciences
Oxadiazoles - pharmacology
Pharmacology. Drug treatments
Physicochemical properties. Structure-activity relationships
Porphyria Ferrochelatase N-Alkylprotophyrm Sydnone Cytochrome P-450 (Chick embryo liver)
Porphyrins - biosynthesis
Protoporphyrins - biosynthesis
Sydnones - pharmacology
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Summary: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 porphyrins. 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-vinylprotoporphyrin IX which inhibits ferrochelatase.
ISSN:0014-5793
1873-3468
DOI:10.1016/0014-5793(86)80289-7