Anthraflavic acid is a potent and specific inhibitor of cytochrome P-448 activity.
Consideration of the computer-optimised dimensions of anthraflavic acid indicates that it is essentially a planar molecule with a large area/depth ratio, that would preferentially interact with the polycyclic aromatic hydrocarbon-induced family of cytochrome P-450 proteins (cytochromes P-448). Anthraflavic acid was a potent inhibitor of the O-deethylations of ethoxycoumarin and ethoxyresorufin, both catalysed primarily by cytochromes P-448, in Arochlor-1254-induced hepatic microsomes. Similarly anthraflavic acid markedly inhibited the mutagenicity of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-I) in the Ames test. In contrast, it has no effect on the dealkylation of pentoxyresorufin, a reaction catalysed primarily by the phenobarbital-induced cytochromes P-450, and NADPH-dependent reduction of cytochrome c. It is concluded that anthraflavic acid is a potent and specific inhibitor of cytochrome P-448 activity.
Biochemistry Department, University of Surrey, Guildford, U.K.
A D
AD
Ayrton
D F
DF
Lewis
C
C
Ioannides
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R
Walker
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D003198:Computer Simulation; D003374:Coumarins / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000037:antagonists & inhibitors*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008958:Models, Molecular; D009249:NADP / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000880:Anthraquinones; D003374:Coumarins; D003580:Cytochromes; D010078:Oxazines; C017299:7-ethoxycoumarin; D009249:NADP; C007649:ethoxyresorufin; D006899:Mixed Function Oxygenases; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; C034889:2,6-dihydroxyanthraquinone