Effects of 6-paradol, an unsaturated ketone from gingers, on cytochrome P450-mediated drug metabolism.
Effects of 6-paradol, an unsaturated ketone from gingers, on cytochrome P450-mediated drug metabolism.
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DOI：
10.1016/j.bmcl.2017.02.047
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发表时间：
2017-04
影响因子：
2.7
通讯作者：
Hyeon Kim;In Sook Kim;S. Rehman;S. Ha;Katsunori Nakamura;H. Yoo
中科院分区：
文献类型：
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作者：
Hyeon Kim;In Sook Kim;S. Rehman;S. Ha;Katsunori Nakamura;H. Yoo
Paradols 是生姜中姜烯酚生物转化产生的不饱和酮。其中，6-paradol因其抗炎、细胞凋亡和神经保护活性而被作为新候选药物进行研究。在本研究中，利用人肝微粒体和重组 CYP 同工酶研究了 6-paradol 对细胞色素 P450 (CYP) 酶活性的抑制作用。 6-Paradol 对 CYP1A2、CYP2B6、CYP2C8、CYP2C9 和 CYP2C19 同工酶表现出浓度依赖性抑制作用，重组 CYP 同工酶的 IC50 值范围为 3.8 至 21.4 µM。然而，预孵育后抑制作用并未增强，表明 6-paradol 不是基于机制的抑制剂。这些结果表明6-paradol可能会发生药代动力学药物相互作用，这是新药开发过程中必须考虑的问题。
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 IC50values 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.