Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia mangostana.
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).
Ryu
Hyung Won
HW
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.
Curtis-Long
Marcus J
MJ
Jung
Sunin
S
Jin
Young Min
YM
Cho
Jung Keun
JK
Ryu
Young Bae
YB
Lee
Woo Song
WS
Park
Ki Hun
KH
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*
D004791:Enzyme Inhibitors; D010936:Plant Extracts; D044004:Xanthones; C000590991:mangostenone F; D009439:Neuraminidase