title: In vitro inhibitory effect of luotonin A on human CYP1A.
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 IC(50) 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea.
authors.forename: Yurngdong
authors.initials: Y
authors.lastname: Jahng
authors.forename: Oh Kwang
authors.initials: OK
authors.lastname: Kwon
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
mesh_terms: D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors; D011758:Pyrroles; D011809:Quinones; C480761:luotonin A; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2