Biotransformation of Benfluron by Rat Hepatic Cytochrome P450. Identification of Individual CYP-Enzymes Involved in Biotransformation of Benfluron, Prospective Antineoplastic Based on Benzo[c]fluorene

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Title:Biotransformation of Benfluron by Rat Hepatic Cytochrome P450. Identification of Individual CYP-Enzymes Involved in Biotransformation of Benfluron, Prospective Antineoplastic Based on Benzo[c]fluorene
Creators:
Hrubý, Kamil
Anzenbacherová, Eva
Anzenbacher, Pavel
Nobilis, Milan
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 65, 8, pp. 1374-1386
Uncontrolled Keywords:Antitumor activity, Metabolism, Biotransformations, Benzo[<i>c</i>]fluorenes, Microsomes, Cytochrome P450

Abstract

Benfluron, 5-[2-(dimethylamino)ethoxy]-7<i>H</i>-benzo[<i>c</i>]fluoren-7-one hydrochloride, a prospective antineoplastic agent, is metabolised by cytochromes P450 to <i>N</i>-demethyl and 9-hydroxy derivatives. To prove the participation of individual cytochrome P450 isoforms in formation of these metabolites, selective induction of cytochromes P450, inhibition of benfluron biotransformation using inhibitors specific for individual cytochromes P450, and inhibition by benfluron of "marker" enzyme activities characteristic of certain cytochromes P450 were used. <i>N</i>-Demethylbenfluron appears to be formed mainly by the cytochromes P450 of the 3A, 2B and 2C subfamilies with possible participation of the isoform 2E1; 9-hydroxybenfluron is formed with participation of cytochromes P450 belonging to 1A, and most probably to 3A and 2E1 enzymes. The fact that benfluron is in this respect a relatively promiscuous substrate may be an advantage because its metabolism should not be influenced by the absence or low activity of some cytochrome P450 isoforms and by possible drug interactions. <p>

Title:Biotransformation of Benfluron by Rat Hepatic Cytochrome P450. Identification of Individual CYP-Enzymes Involved in Biotransformation of Benfluron, Prospective Antineoplastic Based on Benzo[c]fluorene
Creators:
Hrubý, Kamil
Anzenbacherová, Eva
Anzenbacher, Pavel
Nobilis, Milan
Uncontrolled Keywords:Antitumor activity, Metabolism, Biotransformations, Benzo[<i>c</i>]fluorenes, Microsomes, Cytochrome P450
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:65
Number:8
Page Range:pp. 1374-1386
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20001374UNSPECIFIED
ID Code:1722
Item Type:Article
Deposited On:06 Feb 2009 17:12
Last Modified:06 Feb 2009 16:12

Citation

Hrubý, Kamil; Anzenbacherová, Eva; Anzenbacher, Pavel; Nobilis, Milan (2000) Biotransformation of Benfluron by Rat Hepatic Cytochrome P450. Identification of Individual CYP-Enzymes Involved in Biotransformation of Benfluron, Prospective Antineoplastic Based on Benzo[c]fluorene. Collection of Czechoslovak Chemical Communications, 65 (8). pp. 1374-1386. ISSN 0010-0765

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