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 mu M) and CYP2C11 inhibitors (K(i) = 91-118 mu M). Dihydrotanshinone was not only a noncompetitive inhibitor of CYP3A2 (K(i)= 110 mu M), but also a competitive CYP2C11 inhibitor (K(i) = 55 mu M). 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. (C) 2011 Elsevier B.V. All rights reserved.