In vitro inhibitory effect of luotonin A on human CYP1A

Title
In vitro inhibitory effect of luotonin A on human CYP1A
Author(s)
장영동Lee, Sangkyu[Lee, Sangkyu]Kwon Oh Kwang[Kwon Oh Kwang]
Keywords
ANTICANCER AGENTS; RUTAECARPINE; CAMPTOTHECIN; TRYPTANTHRIN; ALKALOIDS; ENZYMES
Issue Date
201212
Publisher
PHARMACEUTICAL SOC KOREA
Citation
ARCHIVES OF PHARMACAL RESEARCH, v.35, no.12, pp.2199 - 2203
Abstract
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.
URI
http://hdl.handle.net/YU.REPOSITORY/26694http://dx.doi.org/10.1007/s12272-012-1218-0
ISSN
0253-6269
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약학대학 > 약학부 > Articles
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