Inhibitory effect of tanshinones on rat CYP3A2 and CYP2C11 activity and its structure-activity relationship.
This study investigated the effect of tanshinones on rat liver microsomal CYP3A2 and 2C11 activity and explored the structure-activity relationship of tanshinones with CYP3A activity. Cryptotanshinone, tanshinone I and tanshinone IIA were competitive CYP3A2 inhibitors (K(i) = 199-243 μM) and CYP2C11 inhibitors (K(i) = 91-118 μM). Dihydrotanshinone was not only a noncompetitive inhibitor of CYP3A2 (K(i) = 110 μM), but also a competitive CYP2C11 inhibitor (K(i) = 55 μM). The structural difference between dihydrotanshinone and tanshinone I at C-15 position of furan ring resulted in the different modes of inhibition on CYP3A activity.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China. usxinwang@gmail.com
Xin
X
Wang
John H K
JH
Yeung
D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D000072467:Cytochrome P450 Family 2; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006900:Hydroxylation; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry; D039181:Steroid 16-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000378:metabolism
D045784:Abietanes; D065692:Cytochrome P-450 CYP3A Inhibitors; D004365:Drugs, Chinese Herbal; D008565:Membrane Proteins; D010616:Phenanthrenes; C021751:tanshinone; D013739:Testosterone; C037886:cryptotanshinone; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase