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 (Ki = 199–243 μM) and CYP2C11 inhibitors (Ki = 91–118 μM). Dihydrotanshinone was not only a noncompetitive inhibitor of CYP3A2 (Ki = 110 μM), but also a competitive CYP2C11 inhibitor (Ki = 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.

Graphical AbstractThe structural difference between dihydrotanshinone and tanshinone I is only the presence of double bond at C-15 position of furan ring, but this resulted in the different mode of inhibition on rat CYP3A activity.Figure optionsDownload as PowerPoint slide