Psoralen, a mechanism-based inactivator of CYP2B6

Chemico-biological Interactions
Lin JiJiang Zheng

Abstract

Furanocoumarin compound psoralen (PRN) is a major active ingredient found in herbaceous plants. PRN has been used for the treatment of various dermal diseases in China. We evaluated the inhibitory effect of PRN on cytochrome P450 2B6 (CYP2B6) and found that PRN induced a time-, concentration-, and NADPH-dependent inactivation of CYP2B6 with the values of KI and kinact being 110.2 μM and 0.200 min(-1), respectively. Ticlopidine, a CYP2B6 substrate, prevented the enzyme from the inactivation induced by PRN. Exogenous nucleophile glutathione (GSH) and catalase/superoxide dismutase showed limited protection of CYP2B6 from the inactivation. The estimated partition ratio of the inactivation was approximately 400. GSH trapping experiments indicates that an epoxide or/and γ-ketoenal intermediate was formed in microsomal incubations with PRN. In summary, PRN was characterized as a mechanism-based inactivator of CYP2B6.

References

Sep 1, 1993·Chemical Research in Toxicology·K L Kunze, W F Trager
May 5, 1998·Chemical Research in Toxicology·K HeP F Hollenberg
Jul 17, 1998·Biochemistry·L L Koenigs, W F Trager
Aug 22, 2001·Current Drug Metabolism·U M KentP F Hollenberg
Oct 16, 2001·Antimicrobial Agents and Chemotherapy·H KatsuraM Kobayashi
Jun 20, 2003·Neuropharmacology·Sharon MiksysRachel F Tyndale
Aug 19, 2007·The New England Journal of Medicine·Robert S Stern
Mar 11, 2008·Biochemical Pharmacology·Gang ZhaoLi-He Guo
Jan 10, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·Yi WangHai-Bin Qu
Sep 1, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Chitra SridarPaul F Hollenberg
Nov 16, 2012·Drug Metabolism and Drug Interactions·Miia Turpeinen, Ulrich M Zanger
Aug 27, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xiao-Mei ZhuangChuang Lu
Dec 17, 2014·Chemico-biological Interactions·Jiaojiao CaoJiang Zheng
Feb 26, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals

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Citations

Nov 30, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yan ChenJiang Zheng
Aug 27, 2019·Drug Metabolism Reviews·Bo Wen, Peter Gorycki
Oct 6, 2020·Frontiers in Pharmacology·Yali RenCheng Peng
Oct 13, 2020·Frontiers in Pharmacology·Yunfang ZhouWeiwen Qiu
Jun 27, 2019·Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry·Joazaizulfazli JamalisTaibi Ben Hadda
Jan 22, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Feng ZhangGuang-Bo Ge
May 22, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Ying LiuJiang Zheng

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