Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies


KHAN M. T. H. , Orhan I., Senol F. S. , Kartal M. , Sener B., DVORSKA M., ...Daha Fazla

CHEMICO-BIOLOGICAL INTERACTIONS, cilt.181, ss.383-389, 2009 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 181 Konu: 3
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1016/j.cbi.2009.06.024
  • Dergi Adı: CHEMICO-BIOLOGICAL INTERACTIONS
  • Sayfa Sayıları: ss.383-389

Özet

Flavonoids are one of the largest classes of plant secondary metabolites and are known to possess a number of significant biological activities for human health. In this study, we examined in vitro acetylcholinesterase (ACH) and butyrylcholinesterase (BChE) inhibitory activities of four flavonoid derivatives - quercetin, rutin, kaempferol 3-O-beta-D-galactoside and macluraxanthone. The in vitro results showed that quercetin and macluraxanthone displayed a concentration-dependant inhibition of AChE and BChE. Macluraxanthone showed to be the most potent and specific inhibitor of both the enzymes having the IC(50) values of 8.47 and 29.8 mu M, respectively. The enzyme kinetic studies revealed that quercetin inhibited both the enzymes in competitive manner, whereas the mode of inhibition of macluraxanthone was noncompetitive against AChE and competitive against BChE. The inhibitory profiles of the compounds have been compared with standard AChE inhibitor galanthamine. To get insight of the intermolecular interactions, the molecular docking studies of these two compounds were performed at the active site 3D space of both the enzymes, using ICM-Dock (TM) module. Docking studies exhibited that macluraxanthone binds much more tightly with both the enzymes than quercetin. The calculated docking and binding energies also supported the in vitro inhibitory profiles (IC(50) values). Both the compounds showed several strong hydrogen bonds to several important amino acid residues of both the enzymes. A number of hydrophobic interactions could also explain the potency of the compounds to inhibit AChE and BChE. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved.