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Coumarin substrates for cytochrome P450 2D6 fluorescence assays.
Anal Biochem. 2001 May 15; 292(2):280-6.AB

Abstract

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.

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Authors+Show Affiliations

Nakamura K
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Hanna IH
No affiliation info available
Cai H
No affiliation info available
Nishimura Y
No affiliation info available
Williams KM
No affiliation info available
Guengerich FP
No affiliation info available

MeSH

Amino Acid SequenceCatalysisCoumarinsCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsEnzyme InhibitorsFluorescent DyesHumansKineticsMicrosomes, LiverMolecular Sequence DataQuinidineRecombinant ProteinsSubstrate Specificity

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11355862

Citation

Nakamura, K, et al. "Coumarin Substrates for Cytochrome P450 2D6 Fluorescence Assays." Analytical Biochemistry, vol. 292, no. 2, 2001, pp. 280-6.
Nakamura K, Hanna IH, Cai H, et al. Coumarin substrates for cytochrome P450 2D6 fluorescence assays. Anal Biochem. 2001;292(2):280-6.
Nakamura, K., Hanna, I. H., Cai, H., Nishimura, Y., Williams, K. M., & Guengerich, F. P. (2001). Coumarin substrates for cytochrome P450 2D6 fluorescence assays. Analytical Biochemistry, 292(2), 280-6.
Nakamura K, et al. Coumarin Substrates for Cytochrome P450 2D6 Fluorescence Assays. Anal Biochem. 2001 May 15;292(2):280-6. PubMed PMID: 11355862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coumarin substrates for cytochrome P450 2D6 fluorescence assays. AU - Nakamura,K, AU - Hanna,I H, AU - Cai,H, AU - Nishimura,Y, AU - Williams,K M, AU - Guengerich,F P, PY - 2001/5/18/pubmed PY - 2001/7/20/medline PY - 2001/5/18/entrez SP - 280 EP - 6 JF - Analytical biochemistry JO - Anal Biochem VL - 292 IS - 2 N2 - 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. SN - 0003-2697 UR - https://www.unboundmedicine.com/medline/citation/11355862/Coumarin_substrates_for_cytochrome_P450_2D6_fluorescence_assays_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-2697(01)95098-5 DB - PRIME DP - Unbound Medicine ER -