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KMID : 0043320120350122199
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Archives of Pharmacal Research
2012 Volume.35 No. 12 p.2199 ~ p.2203
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In vitro inhibitory effect of luotonin A on human CYP1A
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Jahng Yurng Dong
Kwon Oh-Kwang
Lee Sang-Kyu
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Abstract
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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 μM 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.
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KEYWORD
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Luotonin A, Inhibition, In vitro, Human liver microsomes, CYP1A1, CYP1A2
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