Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cells, Cultured
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Chick Embryo
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Cytochrome P-450 Enzyme System / physiology
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Dicarbethoxydihydrocollidine / pharmacology
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Ferrochelatase / antagonists & inhibitors*
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Liver / drug effects
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Liver / metabolism*
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Lyases / antagonists & inhibitors*
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Oxadiazoles / pharmacology*
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Porphyrins / biosynthesis*
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Protoporphyrins / biosynthesis
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Sydnones / pharmacology*
Substances
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Oxadiazoles
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Porphyrins
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Protoporphyrins
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Sydnones
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3-(2-(2,4,6-trimethylphenyl)thioethyl)-4-methylsydnone
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Dicarbethoxydihydrocollidine
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Cytochrome P-450 Enzyme System
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protoporphyrin IX
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Lyases
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Ferrochelatase