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Zhang T, Rao J, Li W, et al. Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation. Drug Metab Rev. 2020;52(4):501-530doi: 10.1080/03602532.2020.1828910.
Zhang, T., Rao, J., Li, W., Wang, K., & Qiu, F. (2020). Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation. Drug metabolism reviews, 52(4), 501-530. https://doi.org/10.1080/03602532.2020.1828910
Zhang, Tingting, et al. "Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation." Drug metabolism reviews vol. 52,4 (2020): 501-530. doi: https://doi.org/10.1080/03602532.2020.1828910
Zhang T, Rao J, Li W, Wang K, Qiu F. Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation. Drug Metab Rev. 2020 Nov;52(4):501-530. doi: 10.1080/03602532.2020.1828910. Epub 2020 Oct 12. PMID: 33043714.
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Drug Metab Rev. 2020 Nov;52(4):501-530. doi: 10.1080/03602532.2020.1828910. Epub 2020 Oct 12.

Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation.

Drug metabolism reviews

Tingting Zhang, Jinqiu Rao, Wei Li, Kai Wang, Feng Qiu

Affiliations

  1. School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, P.R. China.
  2. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, P.R. China.
  3. Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.

PMID: 33043714 DOI: 10.1080/03602532.2020.1828910

Abstract

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

Keywords: DDI; P450 enzymes; covalent binding; mechanism-based inactivation; metabolic activation; natural products

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