A Comparison of the In Vitro Inhibitory Effects of Thelephoric Acid and SKF-525A on Human Cytochrome P450 Activity

被引:4
作者
Song, Min [1 ]
Do, HyunHee [1 ]
Kwon, Oh Kwang [1 ]
Yang, Eun-Ju [1 ]
Bee, Jong-Sup [1 ]
Jeong, Tae Cheon [2 ]
Song, Kyung-Sik [1 ]
Lee, Sangkyu [1 ]
机构
[1] Kyungpook Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Taegu 702701, South Korea
[2] Yeungnam Univ, Coll Pharm, Kyongsan 712749, South Korea
基金
新加坡国家研究基金会;
关键词
Thelephoric acid; Polyozellin; SKF-525A; Cytochrome P450; Non-specific inhibitor; HUMAN LIVER-MICROSOMES; PROLYL ENDOPEPTIDASE; DRUG-METABOLISM; MODULATION; INSIGHTS; 2A6;
D O I
10.4062/biomolther.2013.107
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (GYP) 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 GYP isoforms (IC50 values, 3.2-33.7 mu M). Dixon plots of GYP 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 GYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of GYP enzymes on the metabolism of given compounds.
引用
收藏
页码:155 / 160
页数:6
相关论文
共 21 条
[1]  
[Anonymous], 2006, GUIDANCE IND DRUG IN
[2]  
CHANG TKH, 1995, J PHARMACOL EXP THER, V274, P270
[3]   Oxidation of ranitidine by isozymes of flavin-containing monooxygenase and cytochrome P450 [J].
Chung, WG ;
Park, CS ;
Roh, HK ;
Lee, WK ;
Cha, YN .
JAPANESE JOURNAL OF PHARMACOLOGY, 2000, 84 (02) :213-220
[4]   Structure, Function, Regulation and Polymorphism of Human Cytochrome P450 2A6 [J].
Di, Yuan Ming ;
Chow, Vivian Deh-Wei ;
Yang, Li-Ping ;
Zhou, Shu-Feng .
CURRENT DRUG METABOLISM, 2009, 10 (07) :754-780
[5]  
Emoto Chie, 2003, Drug Metab Pharmacokinet, V18, P287, DOI 10.2133/dmpk.18.287
[6]   2-Diethylaminoethyl-2,2-diphenylvalerate-HCl (SKF525A) Revisited: Comparative Cytochrome P450 Inhibition in Human Liver Microsomes by SKF525A, Its Metabolites, and SKF-Acid and SKF-Alcohol [J].
Franklin, Michael R. ;
Hathaway, Laura B. .
DRUG METABOLISM AND DISPOSITION, 2008, 36 (12) :2539-2546
[7]  
Guengerich F P, 1997, Adv Pharmacol, V43, P7, DOI 10.1016/S1054-3589(08)60200-8
[8]   Modulation of cyclophosphamide-based cytochrome P450 gene therapy using liver P450 inhibitors [J].
Huang, ZQ ;
Waxman, DJ .
CANCER GENE THERAPY, 2001, 8 (06) :450-458
[9]   Polyozellin, a new inhibitor of prolyl endopeptidase from Polyozellus multiplex [J].
Hwang, JS ;
Song, KS ;
Kim, WG ;
Lee, TH ;
Koshino, H ;
Yoo, ID .
JOURNAL OF ANTIBIOTICS, 1997, 50 (09) :773-777
[10]   In vitro inhibitory effect of luotonin A on human CYP1A [J].
Jahng, Yurngdong ;
Kwon, Oh Kwang ;
Lee, Sangkyu .
ARCHIVES OF PHARMACAL RESEARCH, 2012, 35 (12) :2199-2203