Isolation of two N-monosubstituted protoporphyrins, bearing either the whole drug or a methyl group on the pyrrole nitrogen atom, from liver of mice given griseofulvin.
1. A hepatic green pigment with inhibitory properties towards the enzyme ferrochelatase has been isolated from the liver of mice treated with griseofulvin and identified as N-methylprotoporphyrin. 2. All four structural isomers of N-methylprotoporphyrin have been demonstrated to be present, NA, where ring A of protoporphyrin IX is N-methylated, being the predominant isomer. 3. In addition to N-methylprotoporphyrin, a second green pigment, present in far greater amounts, was also isolated from the liver of griseofulvin-treated mice. This second green pigment is also an N-monosubstituted protoporphyrin, but in this case the substituent on the pyrrole nitrogen atom appears to be intact griseofulvin rather than a methyl group. 4. The fragmentation of this adduct in tandem m.s. studies suggests that griseofulvin is bound to the pyrrole nitrogen through one of its carbon atoms and further suggests that N-methylprotoporphyrin may arise as a secondary product from the major griseofulvin pigment.
Holley
A E
AE
Biochemical Mechanisms Section, Medical Research Council Laboratories, Carshalton, Surrey, U.K.
Frater
Y
Y
Gibbs
A H
AH
De Matteis
F
F
Lamb
J H
JH
Farmer
P B
PB
Naylor
S
S
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006118:Griseofulvin / Q000008:administration & dosage*; D008099:Liver / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D051379:Mice; D009584:Nitrogen / Q000737:chemistry; D011524:Protoporphyrins / Q000302:isolation & purification*
D011524:Protoporphyrins; D006118:Griseofulvin; D009584:Nitrogen