Coumarin substrates for cytochrome P450 2D6 fluorescence assays.

Nakamura K, Hanna IH, Cai H, Nishimura Y, Williams KM, Guengerich FP
Anal Biochem. 2001 292 (2): 280-6

PMID: 11355862 · DOI:10.1006/abio.2001.5098

A set of nine 4-aminomethyl-7-alkoxycoumarin derivatives was synthesized and characterized as substrates for O-dealkylation by recombinant cytochrome P450 2D6, a major human enzyme involved in drug metabolism. Enzymatic O-dealkylation yields 7-hydroxycoumarins, which have useful fluorescence properties. The substrates, which differed in substitution at the amino and 7-hydroxy positions, varied in terms of catalytic efficiency of O-dealkylation and in their selectivity as substrates for cytochrome P450 2D6 in human liver microsomes. Several of the compounds are useful as cytochrome P450 2D6 substrates in single-phase, rapid-throughput assays.

Copyright 2001 Academic Press.

MeSH Terms (14)

Amino Acid Sequence Catalysis Coumarins Cytochrome P-450 CYP2D6 Cytochrome P-450 CYP2D6 Inhibitors Enzyme Inhibitors Fluorescent Dyes Humans Kinetics Microsomes, Liver Molecular Sequence Data Quinidine Recombinant Proteins Substrate Specificity

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