Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata = 꾸지뽕나무 뿌리로 부터 뉴라미니데이즈 저해제인 잔톤화합물의 개발

Cited 48 time in scopus
Metadata Downloads
Title
Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata = 꾸지뽕나무 뿌리로 부터 뉴라미니데이즈 저해제인 잔톤화합물의 개발
Author(s)
Young Bae Ryu; M J Curtis-Long; J W Lee; J H Kim; J Y Kim; K Y Kang; Woo Song Lee; K H Park
Bibliographic Citation
Bioorganic & Medicinal Chemistry, vol. 17, no. 7, pp. 2744-2750
Publication Year
2009
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 (IC50 = 0.08 ± 0.01 μM), a 200-fold increase in activity relative to that of the first reported xanthone-derived neuraminidase inhibitor, mangiferin (IC50 = 16.2 ± 4.2 μM). 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 μM), whereas other compounds (1-3 and 6-8) showed nanomolar activity (0.08-0.27 μM) 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.
Keyword
2vk6Cudrania tricuspidataNeuraminidaseTime-dependentXanthone
ISSN
0968-0896
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bmc.2009.02.042
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.