Flavonoids as inhibitors of rat liver monooxygenase activities.
Flavanone and six hydroxylated derivatives, and cianidanol and eight ethers and esters thereof, were investigated as inhibitors of cytochrome P-450 mediated reactions in rat liver microsomes. The IC50 values towards aminopyrine N-demethylation varied over a 20-fold range and were shown to depend on the pattern of hydroxylation (flavanone derivatives) and on lipophilicity (cianidanol derivatives). In the latter case, a bilinear relationship exists, the optimal log P being 2.92. Using selected compounds, IC50, Km and Vmax values were determined for aminopyrine N-demethylation, biphenyl 4-hydroxylation, and biphenyl 2-hydroxylation. Depending on the inhibitor and on the activity examined, non-competitive, competitive, or mixed inhibition was seen. Interaction with cytochrome P-450 was also studied spectrally and was always found to result in a modified type II difference spectrum (ligand binding). A dual binding mode is postulated, involving electrostatic and lipophilic interactions.[1]References
- Flavonoids as inhibitors of rat liver monooxygenase activities. Beyeler, S., Testa, B., Perrissoud, D. Biochem. Pharmacol. (1988) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg