RESUMO
Two effective cytochrome P450 (CYP) inhibitors were isolated from tarragon, Artemisia dracunculus. Their structures were spectroscopically identified as 2E,4E-undeca-2,4-diene-8,10-diynoic acid isobutylamide (1) and 2E,4E-undeca-2,4-diene-8,10-diynoic acid piperidide (2). Both compounds had dose-dependent inhibitory effects on CYP3A4 activity with IC50 values of 10.0 ± 1.3 µM for compound 1 and 3.3 ± 0.2 µM for compound 2, and exhibited mechanism-based inhibition. This is the first reported isolation of effective CYP inhibitors from tarragon (Artemisia dracunculus) purchased from a Japanese market.
Assuntos
Artemisia/química , Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/química , Ácidos Graxos Insaturados/química , Piperidinas/química , Extratos Vegetais/química , Sistema Enzimático do Citocromo P-450/química , Inibidores Enzimáticos/isolamento & purificação , Ácidos Graxos Insaturados/isolamento & purificação , Isoenzimas/antagonistas & inibidores , Isoenzimas/química , Cinética , NADP/química , Piperidinas/isolamento & purificação , SoluçõesRESUMO
A highly polymethylated flavone that effectively inhibited cytochrome P450s (CYPs) 1A2 and 3A4 (IC(50) = 2.41 and 1.71 µM) in vitro was isolated from thyme leaves (Thymus saturoides) purchased from a Japanese market. Its structure was spectroscopically identified as 4',5-dihydroxy-3',6,7,8-tetramethoxy flavone (8-methoxycirsilineol, 1). This is the first report describing a strong inhibitor of CYP1A2 and 3A4 isolated from Thymus saturoides.
