In vitro inhibitory effect of luotonin A on human CYP1A

被引：7
|
作者：
Jahng, Yurngdong [2 ]
Kwon, Oh Kwang [1 ]
Lee, Sangkyu [1 ]
机构：
[1] Kyungpook Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Taegu 702701, South Korea
[2] Yeungnam Univ, Coll Pharm, Gyongsan 712749, South Korea
来源：
ARCHIVES OF PHARMACAL RESEARCH | 2012年 / 35卷 / 12期
关键词：
Luotonin A; Inhibition; In vitro; Human liver microsomes; CYP1A1; CYP1A2; ANTICANCER AGENTS; RUTAECARPINE; CAMPTOTHECIN; TRYPTANTHRIN; ALKALOIDS; ENZYMES;
D O I：
10.1007/s12272-012-1218-0
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Luotonin A, a pyrroloquinolinequinoline alkaloid, is a natural inhibitor of topoisomerase I. In the present study, cytochrome P450 (CYP) inhibition by luotonin A was examined in pooled human liver microsomes (HLMs) and human recombinant cDNA-expressed human CYPs using a cocktail probe assay to investigate potential drug-drug interactions. Luotonin A selectively inhibited CYP1A2-catalyzed phenacetin O-deethylation with an IC50 of 6.3 mu M in HLMs, and strongly decreased CYP1A2-catalyzed phenacetin O-deethylation dose-dependently in HLMs, but did not inhibit it time-dependently. Furthermore, the Lineweaver-Burk and secondary plots for the inhibition of CYP1A2 in HLMs well fitted competitive inhibition mode. Luotonin A showed the selectivity of inhibitory effects on CYP1A1 and CYP1A2 in human recombinant cDNA-expressed CYP 1A1 and 1A2, respectively. Luotonin A was found to be a potent CYP1A inhibitor that might cause drug-drug interactions when co-administrated with CYP1A substrates.
引用
收藏
页码：2199 / 2203
页数：5
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