Planta Med 2009; 75(2): 137-141
DOI: 10.1055/s-0028-1088350
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of CYP1A1 by Quassinoids Found in Picrasma excelsa

Mario Shields1 , Umar Niazi2 , Simone Badal1 , Trevor Yee1 , Michael J. Sutcliffe2 , Rupika Delgoda1
  • 1Natural Products Institute, Faculty of Pure and Applied Sciences, University of the West Indies, Mona, Jamaica, West Indies
  • 2School of Chemical Engineering and Analytical Science & Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, U.K.
Further Information

Publication History

Received: January 25, 2008 Revised: September 22, 2008

Accepted: September 29, 2008

Publication Date:
18 November 2008 (online)

Abstract

Infusions of the plant Picrasma excelsa, known as Jamaican bitterwood tea, are commonly consumed to lower blood sugar levels in diabetics who are already on prescription medicines. We therefore investigated the inhibition properties of this tea against a panel of cytochrome P450 (CYP) enzymes, which are primarily responsible for the metabolism of a majority of drugs on the market. The two major ingredients, quassin and neoquassin, were then isolated and used for further characterization. Inhibition of the activities of heterologously expressed CYP microsomes (CYPs 2D6, 3A4, 1A1, 1A2, 2C9, and 2C19) was monitored, and the most potent inhibition was found to be against CYP1A1, with IC50 values of 9.2 μM and 11.9 μM for quassin and neoquassin, respectively. The moderate inhibition against the CYP1A1 isoform by quassin and neoquassin displayed partial competitive inhibition kinetics, with inhibition constants (K i) of 10.8 ± 1.6 μM, for quassin and competitive inhibition kinetics, with a K i of 11.3 ± 0.9 μM, for neoquassin. We then docked these two inhibitors into the active site of a model of CYP1A1, which provided insight at the atomic level into the structure-activity relationship of quassinoids with respect to this important CYP isoform known to be an activator of carcinogens, thus providing a useful basis for the search for more potent inhibitors of CYP1A1 that may have implications in chemoprotection.

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Dr. Rupika Delgoda

Natural Products Institute

Faculty of Pure and Applied Sciences

University of the West Indies

6 Belmopan Close

Mona

Jamaica

West Indies

Phone: +876 970-2574

Fax: +876 970-2574

Email: thejani.delgoda@uwimona.edu.jm

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