title: Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata.
abstract: Natural polyphenolic compounds generally transpire to show relatively low inhibition against glycosidase including neuraminidase. In addition the inhibition modes of such compounds are rarely competitive. In this manuscript, a series of xanthone derivatives from Cudrania tricuspidata are shown to display nanomolar inhibitor activity against neuraminidase (EC 3.2.1.18) as well as competitive inhibition modes. Compound 8 bearing vicinal dihydroxy group on the A-ring displays nanomolar activity (IC(50)=0.08+/-0.01 microM), a 200-fold increase in activity relative to that of the first reported xanthone-derived neuraminidase inhibitor, mangiferin (IC(50)=16.2+/-4.2 microM). The 6,7-vicinal dihydroxy group plays a crucial role for inhibitory activity because compound 4, which has one of these hydroxyl groups prenylated was inactive (33% at 200 microM), whereas other compounds (1-3 and 6-8) showed nanomolar activity (0.08-0.27 microM) and competitive inhibition modes. Interestingly all inhibitors manifested enzyme isomerization inhibition against neuraminidase. The most potent inhibitor, compound 8 showed similar interaction with a transition-state analogue of neuraminic acid in active site.
authors.affiliation: Division of Applied Life Science (BK21 program), EB-NCRC, Institute of Agriculture and Life Science, Graduate School of Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Curtis-Long
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Jin Hyo
authors.initials: JH
authors.lastname: Kim
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Kyu Young
authors.initials: KY
authors.lastname: Kang
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
mesh_terms: D020134:Catalytic Domain; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007700:Kinetics; D029586:Moraceae / Q000737:chemistry*; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D044004:Xanthones; D009439:Neuraminidase