A Comparison of the In Vitro Inhibitory Effects of Thelephoric Acid and SKF-525A on Human Cytochrome P450 Activity.
- Author:
Min SONG
1
;
Hyunhee DO
;
Oh Kwang KWON
;
Eun Ju YANG
;
Jong Sup BAE
;
Tae Cheon JEONG
;
Kyung Sik SONG
;
Sangkyu LEE
Author Information
1. College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. sangkyu@knu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Thelephoric acid;
Polyozellin;
SKF-525A;
Cytochrome P450;
Non-specific inhibitor
- MeSH:
Cytochrome P-450 CYP1A2;
Cytochrome P-450 CYP2D6;
Cytochrome P-450 CYP2E1;
Cytochrome P-450 Enzyme System*;
Humans;
Hydrolysis;
Metabolism;
Microsomes, Liver;
Proadifen*;
Protein Isoforms
- From:Biomolecules & Therapeutics
2014;22(2):155-160
- CountryRepublic of Korea
- Language:English
-
Abstract:
Thelephoric acid is an antioxidant produced by the hydrolysis of polyozellin, which is isolated from Polyozellus multiplex. In the present study, the inhibitory effects of polyozellin and thelephoric acid on 9 cytochrome P450 (CYP) family members (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) were examined in pooled human liver microsomes (HLMs) using a cocktail probe assay. Polyozellin exhibited weak inhibitory effects on the activities of all 9 CYPs examined, whereas thelephoric acid exhibited dose- and time-dependent inhibition of all 9 CYP isoforms (IC50 values, 3.2-33.7 muM). Dixon plots of CYP inhibition indicated that thelephoric acid was a competitive inhibitor of CYP1A2 and CYP3A4. In contrast, thelephoric acid was a noncompetitive inhibitor of CYP2D6. Our findings indicate that thelephoric acid may be a novel, non-specific CYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of CYP enzymes on the metabolism of given compounds.
