title: Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia mangostana.
abstract: This study was designed to gain deeper insights into the molecular properties of natural xanthones as neuraminidase inhibitors. A series of xanthones 1-12 was isolated from the seedcases of Garcinia mangostana and evaluated for bacteria neuraminidase inhibitory activity. Compounds 11 and 12 emerged to be new xanthones (mangostenone F, mangostenone G) which we fully spectroscopically characterized. The IC(50) values of compounds 1-12 were determined to range between 0.27-65.7 microM. The most potent neuraminidase inhibitor 10 which has an IC(50) of 270 nM features a 5,8-diol moiety on the B ring. Interestingly, structure-activity studies reveal that these xanthones show different kinetic inhibition mechanisms depending upon the arrangement of hydroxyl groups in the B ring. Compound 6 possessing a 6,7-diol motif on the B-ring operated under the enzyme isomerization model (k(5)=0.1144 microM(-1) s(-1), k(6)=0.001105 s(-1), and K(i)(app)=7.41 microM), whereas compound 10 possessing a 5,8-diol unit displayed simple reversible slow-binding inhibition (k(3)=0.02294 microM(-1) s(-1), k(4)=0.001025 s(-1), and K(i)(app)=0.04468 microM).
authors.affiliation: Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Curtis-Long
authors.forename: Sunin
authors.initials: S
authors.lastname: Jung
authors.forename: Young Min
authors.initials: YM
authors.lastname: Jin
authors.forename: Jung Keun
authors.initials: JK
authors.lastname: Cho
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D029762:Garcinia mangostana / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D009439:Neuraminidase / Q000032:analysis / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D044004:Xanthones; C000590991:mangostenone F; D009439:Neuraminidase