Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation
Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation
复制标题
基于代谢激活的天然产物对细胞色素 P450 酶的灭活机制
DOI：
10.1080/03602532.2020.1828910
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发表时间：
2020-10
影响因子：
5.9
通讯作者：
Feng Qiu
中科院分区：
文献类型：
--
作者：
Tingting Zhang;Jinqiu Rao;Wei Li;Kai Wang;Feng Qiu
细胞色素P450酶（P450酶）是最常见和最重要的I相代谢酶，负责临床药物和其他外源性药物的大部分代谢。当P450酶的活性被抑制时，会发生药物-药物相互作用（ddi）。特别是，与可逆抑制相比，P450酶的不可逆抑制可能导致严重的不良相互作用。许多天然产物已被证明是P450酶的不可逆抑制剂。由于全球天然产品消费的快速增长，摄入天然存在的不可逆P450酶抑制剂的风险一直在上升。不可逆抑制通常被称为基于机制的失活，它依赖于时间、浓度和NADPH。一般来说，亲电中间体的形成是P450酶失活的基础。本文对天然P450酶灭活剂进行了全面分类，包括萜类、苯丙类、黄酮类、生物碱和醌类等。此外，根据文献报道的IC 50（或K i）值的结构-活性相关性以及基于代谢激活的潜在机制也得到了深入的强调。
Cytochrome P450 enzymes (P450 enzymes) are the most common and important phase I metabolic enzymes and are responsible for the majority of the metabolism of clinical drugs and other xenobiotics. Drug-drug interactions (DDIs) can occur when the activities of P450 enzymes are inhibited. In particular, irreversible inhibition of P450 enzymes may lead to severe adverse interactions, compared to reversible inhibition. Many natural products have been shown to be irreversible inhibitors of P450 enzymes. The risks for intake of naturally occurring irreversible P450 enzyme inhibitors have been rising due to the rapid growth of the global consumption of natural products. Irreversible inhibition is usually called mechanism-based inactivation, which is time-, concentration- and NADPH- dependent. Generally, the formation of electrophilic intermediates is fundamental for the inactivation of P450 enzymes. This review comprehensively classifies natural P450 enzyme inactivators, including terpenoids, phenylpropanoids, flavonoids, alkaloids, and quinones obtained from herbs or foods. Moreover, the structure-activity correlations according to the IC 50 (or K i ) values reported in the literature as well as the underlying mechanisms based on metabolic activation are highlighted in depth.
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影响因子：
2
作者：
T. Usia;T. Watabe;S. Kadota;Y. Tezuka
通讯作者：
T. Usia;T. Watabe;S. Kadota;Y. Tezuka
影响因子：
3.6
作者：
Haoming Zhang;Hemali Amunugama;S. Ney;Nyemade Cooper;P. Hollenberg
通讯作者：
Haoming Zhang;Hemali Amunugama;S. Ney;Nyemade Cooper;P. Hollenberg
影响因子：
6.1
作者：
Subehan;S. F. Zaidi;S. Kadota;Y. Tezuka
通讯作者：
Subehan;S. F. Zaidi;S. Kadota;Y. Tezuka
影响因子：
6.7
作者：
I. Tegeder;L. Bräutigam;M. Podda;Silke Meier;R. Kaufmann;G. Geisslinger;M. Grundmann‐Kollmann
通讯作者：
I. Tegeder;L. Bräutigam;M. Podda;Silke Meier;R. Kaufmann;G. Geisslinger;M. Grundmann‐Kollmann
DOI：
10.3109/00498257109112269
发表时间：
1971
期刊：
Xenobiotica; the fate of foreign compounds in biological systems
影响因子：
--
作者：
Michael R. Franklin
通讯作者：
Michael R. Franklin