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Bioorg Med Chem Lett. 2017 Apr 15;27(8):1826-1830. doi: 10.1016/j.bmcl.2017.02.047. Epub 2017 Feb 20.

Effects of 6-paradol, an unsaturated ketone from gingers, on cytochrome P450-mediated drug metabolism.

Author information

1
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan-si, Gyeonggi-do 15588, Republic of Korea.
2
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
3
Korea Food Research Institute, Seongnam, Gyeonggi-do 426-791, Republic of Korea.
4
Department of Pharmacy, Ryukyu University Hospital, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan.
5
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan-si, Gyeonggi-do 15588, Republic of Korea. Electronic address: yoohh@hanyang.ac.kr.

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 21.4µM 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.

KEYWORDS:

6-Paradol; CYP inhibition; Drug-drug interaction; Ginger; Unsaturated ketone

PMID:
28274629
DOI:
10.1016/j.bmcl.2017.02.047
[Indexed for MEDLINE]

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