Effects of 6-paradol, an unsaturated ketone from gingers, on cytochrome P450-mediated drug metabolism. Issue 8 (15th April 2017)

• Record Type: Journal Article
• Authors: Kim, Hyeong Jun; Kim, In Sook; Rehman, Shaheed Ur; Ha, Sang Keun; Nakamura, Katsunori; Yoo, Hye Hyun
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 8(2017)
• Page Start: 1826
• Page End: 1830
• Publication Date: 2017-04-15
• Subjects: 6-Paradol -- Unsaturated ketone -- Ginger -- CYP inhibition -- Drug-drug interaction; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.02.047
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Paradols are unsaturated ketones produced by biotransformation of shogaols in gingers. Among them, 6-paradol has been investigated as a new drug candidate due to its anti-inflammatory, apoptotic, and neuroprotective activities. In this study, the inhibitory effects of 6-paradol on the activities of cytochrome P450 (CYP) enzymes were investigated with human liver microsomes and recombinant CYP isozymes. 6-Paradol showed concentration-dependent inhibitory effects on CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 isozymes, with IC50 values ranging from 3.8 to 21.4 µM in recombinant CYP isozymes. However, the inhibition was not potentiated following pre-incubation, indicating that 6-paradol is not a mechanism-based inhibitor. These results suggest that pharmacokinetic drug-drug interactions might occur with 6-paradol, which must be considered in the process of new drug development.