Inhibitory effect of tanshinones on rat CYP3A2 and CYP2C11 activity and its structure-activity relationship

Xin Wang; John H.K. Yeung

doi:10.1016/j.fitote.2011.01.011

Inhibitory effect of tanshinones on rat CYP3A2 and CYP2C11 activity and its structure-activity relationship

Xin Wang^*
, John H.K. Yeung

^*Corresponding author for this work

Chinese University of Hong Kong
University of Texas Medical Branch at Galveston

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	539-545
Number of pages	7
Journal	Fitoterapia
Volume	82
Issue number	4
DOIs	https://doi.org/10.1016/j.fitote.2011.01.011
State	Published - Jun 2011
Externally published	Yes

Keywords

CYP2C11
CYP3A2
Inhibition
Structure-activity
Tanshinones

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10.1016/j.fitote.2011.01.011

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title = "Inhibitory effect of tanshinones on rat CYP3A2 and CYP2C11 activity and its structure-activity relationship",

abstract = "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.",

keywords = "CYP2C11, CYP3A2, Inhibition, Structure-activity, Tanshinones",

author = "Xin Wang and Yeung, \{John H.K.\}",

year = "2011",

month = jun,

doi = "10.1016/j.fitote.2011.01.011",

language = "英语",

volume = "82",

pages = "539--545",

journal = "Fitoterapia",

issn = "0367-326X",

publisher = "Elsevier B.V.",

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}

TY - JOUR

T1 - Inhibitory effect of tanshinones on rat CYP3A2 and CYP2C11 activity and its structure-activity relationship

AU - Wang, Xin

AU - Yeung, John H.K.

PY - 2011/6

Y1 - 2011/6

N2 - 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.

AB - 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.

KW - CYP2C11

KW - CYP3A2

KW - Inhibition

KW - Structure-activity

KW - Tanshinones

UR - https://www.scopus.com/pages/publications/79955473621

U2 - 10.1016/j.fitote.2011.01.011

DO - 10.1016/j.fitote.2011.01.011

M3 - 文章

C2 - 21262326

AN - SCOPUS:79955473621

SN - 0367-326X

VL - 82

SP - 539

EP - 545

JO - Fitoterapia

JF - Fitoterapia

IS - 4

ER -

Inhibitory effect of tanshinones on rat CYP3A2 and CYP2C11 activity and its structure-activity relationship

Abstract

Keywords

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