Citrusosides A-D and furanocoumarins with cholinesterase inhibitory activity from the fruit peels of Citrus hystrix

Abstract

Four new compounds, citrusosides A-D (1-4), and 15 known compounds were isolated from the hexanes and CH(2)Cl(2) extracts of the peels of Citrus hystrix fruits. Compound 1 is a 1-O-isopropyl-6-O-β-D-glucopyranosyl ester of 5'',9''-dimethyl-2'',8''-decadienoic acid. Compounds 2-4 possess a 1-O-isopropyl-β-D-glucopyranosyl and a dihydroxyprenylfuranocoumarin moiety conjugated to the 3-hydroxy-3-methylglutaric acid as diesters. Several furanocoumarins were evaluated for their cholinesterase inhibitory activity. (R)-(+)-6'-Hydroxy-7'-methoxybergamottin, (R)-(+)-6',7'-dihydroxybergamottin, and (+)-isoimparatorin showed IC(50) values of 11.2 ± 0.1, 15.4 ± 0.3, and 23 ± 0.2 μM, respectively. Bioassay results indicated that the presence of a dioxygenated geranyl chain in the test compounds is crucial for the inhibitory activity.