Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism

Jorge Capdevila, Lionel Gil, Miriam Orellana, Lawrence J. Marnett, J. Ian Mason, Pendri Yadagiri, J R Falck

Research output: Contribution to journalArticle

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Abstract

A new generation of heteroatom analogs of arachidonic acid are documented as powerful and selective inhibitors of the cytochrome P-450-dependent arachidonic acid oxygenase reaction (IC50, 5-10 μm) with little effect on either cyclooxygenase or soybean lipoxidase at 100 μm. The imidazole derivatives, ketoconazole and clotrimazole, are potent and selective inhibitors of the arachidonic acid epoxygenase and lipoxidase-like activities of phenobarbital-induced rat liver microsomal fractions (IC50, 2.0 and 0.3 μm, respectively). In contrast, the ω ωw-1 oxygenase activity of ciprofibrate-induced microsomal fractions was relatively resistant to inhibition by these compounds (IC50, 50 and 25 μm for ketoconazole and clotrimazole, respectively). Nordihydroguaiaretic acid (NDGA), eicosatetraynoic acid (ETYA), and indomethacin, extensively utilized inhibitors of the cyclooxygenase and lipoxygenase branches of the arachidonate cascade, also inhibit cytochrome P-450-dependent arachidonic acid metabolism. In decreasing order of potency, they were NDGA, ETYA, and indomethacin (IC50,15, 40, and 70 μm, respectively).

Original languageEnglish (US)
Pages (from-to)257-263
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume261
Issue number2
DOIs
StatePublished - 1988

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Arachidonic Acid
Metabolism
Masoprocol
Inhibitory Concentration 50
Clotrimazole
Oxygenases
Ketoconazole
Lipoxygenase
Indomethacin
Lipoxygenase Inhibitors
Acids
Cyclooxygenase Inhibitors
Arachidonate Lipoxygenases
Prostaglandin-Endoperoxide Synthases
Phenobarbital
Liver
Cytochrome P-450 Enzyme System
Rats
Soybeans
Derivatives

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism. / Capdevila, Jorge; Gil, Lionel; Orellana, Miriam; Marnett, Lawrence J.; Mason, J. Ian; Yadagiri, Pendri; Falck, J R.

In: Archives of Biochemistry and Biophysics, Vol. 261, No. 2, 1988, p. 257-263.

Research output: Contribution to journalArticle

Capdevila, J, Gil, L, Orellana, M, Marnett, LJ, Mason, JI, Yadagiri, P & Falck, JR 1988, 'Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism', Archives of Biochemistry and Biophysics, vol. 261, no. 2, pp. 257-263. https://doi.org/10.1016/0003-9861(88)90340-2
Capdevila, Jorge ; Gil, Lionel ; Orellana, Miriam ; Marnett, Lawrence J. ; Mason, J. Ian ; Yadagiri, Pendri ; Falck, J R. / Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism. In: Archives of Biochemistry and Biophysics. 1988 ; Vol. 261, No. 2. pp. 257-263.
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