Structure-activity relationships in the effects of 1-alkylimidazoles on microsomal oxidation in vitro and in vivo

C. F. Wilkinson, Krystyna Hetnarski, G. Patricia Cantwell, Frederick J. Di Carlo

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

The inhibitory activity of a series of 13 1-alkylimidazoles toward microsomal epoxidation of aldrin in enzyme preparations from rat liver and armyworm (Prodenia eridania) gut is optimal in compounds with a chain length of 8-10 carbon atoms. The capacity of the imidazoles to bind to cytochrome P-450 (type II) appears to be closely related to their inhibitory activity. The activity of the compounds in vivo in synergizing the toxicity of carbaryl to houseflies and potentiating pentobarbital sleeping time in mice closely parallels the data in vitro. Regression analyses clearly establish that both activity patterns in vitro and in vivo can be satisfactorily described by linear equations in terms of the hydrophobic bonding constant (π and π2) indicating a close correlation between biological activity and lipophilic character.

Original languageEnglish
Pages (from-to)2377-2386
Number of pages10
JournalBiochemical Pharmacology
Volume23
Issue number17
DOIs
StatePublished - Sep 1 1974
Externally publishedYes

Fingerprint

Aldrin
Imidazoles
Carbaryl
Epoxidation
Pentobarbital
Structure-Activity Relationship
Bioactivity
Linear equations
Chain length
Liver
Cytochrome P-450 Enzyme System
Toxicity
Rats
Carbon
Houseflies
Atoms
Oxidation
Enzymes
Regression Analysis
In Vitro Techniques

ASJC Scopus subject areas

  • Pharmacology

Cite this

Structure-activity relationships in the effects of 1-alkylimidazoles on microsomal oxidation in vitro and in vivo. / Wilkinson, C. F.; Hetnarski, Krystyna; Patricia Cantwell, G.; Di Carlo, Frederick J.

In: Biochemical Pharmacology, Vol. 23, No. 17, 01.09.1974, p. 2377-2386.

Research output: Contribution to journalArticle

Wilkinson, C. F. ; Hetnarski, Krystyna ; Patricia Cantwell, G. ; Di Carlo, Frederick J. / Structure-activity relationships in the effects of 1-alkylimidazoles on microsomal oxidation in vitro and in vivo. In: Biochemical Pharmacology. 1974 ; Vol. 23, No. 17. pp. 2377-2386.
@article{7176aa108a054aa79843ffca78e4d1ba,
title = "Structure-activity relationships in the effects of 1-alkylimidazoles on microsomal oxidation in vitro and in vivo",
abstract = "The inhibitory activity of a series of 13 1-alkylimidazoles toward microsomal epoxidation of aldrin in enzyme preparations from rat liver and armyworm (Prodenia eridania) gut is optimal in compounds with a chain length of 8-10 carbon atoms. The capacity of the imidazoles to bind to cytochrome P-450 (type II) appears to be closely related to their inhibitory activity. The activity of the compounds in vivo in synergizing the toxicity of carbaryl to houseflies and potentiating pentobarbital sleeping time in mice closely parallels the data in vitro. Regression analyses clearly establish that both activity patterns in vitro and in vivo can be satisfactorily described by linear equations in terms of the hydrophobic bonding constant (π and π2) indicating a close correlation between biological activity and lipophilic character.",
author = "Wilkinson, {C. F.} and Krystyna Hetnarski and {Patricia Cantwell}, G. and {Di Carlo}, {Frederick J.}",
year = "1974",
month = "9",
day = "1",
doi = "10.1016/0006-2952(74)90227-5",
language = "English",
volume = "23",
pages = "2377--2386",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "17",

}

TY - JOUR

T1 - Structure-activity relationships in the effects of 1-alkylimidazoles on microsomal oxidation in vitro and in vivo

AU - Wilkinson, C. F.

AU - Hetnarski, Krystyna

AU - Patricia Cantwell, G.

AU - Di Carlo, Frederick J.

PY - 1974/9/1

Y1 - 1974/9/1

N2 - The inhibitory activity of a series of 13 1-alkylimidazoles toward microsomal epoxidation of aldrin in enzyme preparations from rat liver and armyworm (Prodenia eridania) gut is optimal in compounds with a chain length of 8-10 carbon atoms. The capacity of the imidazoles to bind to cytochrome P-450 (type II) appears to be closely related to their inhibitory activity. The activity of the compounds in vivo in synergizing the toxicity of carbaryl to houseflies and potentiating pentobarbital sleeping time in mice closely parallels the data in vitro. Regression analyses clearly establish that both activity patterns in vitro and in vivo can be satisfactorily described by linear equations in terms of the hydrophobic bonding constant (π and π2) indicating a close correlation between biological activity and lipophilic character.

AB - The inhibitory activity of a series of 13 1-alkylimidazoles toward microsomal epoxidation of aldrin in enzyme preparations from rat liver and armyworm (Prodenia eridania) gut is optimal in compounds with a chain length of 8-10 carbon atoms. The capacity of the imidazoles to bind to cytochrome P-450 (type II) appears to be closely related to their inhibitory activity. The activity of the compounds in vivo in synergizing the toxicity of carbaryl to houseflies and potentiating pentobarbital sleeping time in mice closely parallels the data in vitro. Regression analyses clearly establish that both activity patterns in vitro and in vivo can be satisfactorily described by linear equations in terms of the hydrophobic bonding constant (π and π2) indicating a close correlation between biological activity and lipophilic character.

UR - http://www.scopus.com/inward/record.url?scp=0016169576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0016169576&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(74)90227-5

DO - 10.1016/0006-2952(74)90227-5

M3 - Article

VL - 23

SP - 2377

EP - 2386

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 17

ER -