Current Bioinformatics

Yi-Ping Phoebe Chen
Department of Computer Science and Information Technology
La Trobe University
Melbourne
Australia

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Putative Molecular Interactions Involving Naturally Occurring Steroidal Alkaloids from Sarcococca hookeriana Against Acetyl- and Butyryl- Cholinesterase

Author(s): Mahmud Tareq Hassan Khan.

Abstract:

A large number of naturally origin alkaloids are reported to be potential against cholinesterases (e.g., acetylcholinesterase, butyrylcholinestarase, etc.). Some of them are from chemical subclass of steroidal alkaloids. Here in this paper docking calculations and the possible intermolecular and atomic interactions have been studied and presented from some of the natural and semisynthetic steroidal alkaloids. These alkaloids were found to be potent inhibitors against both the acetyl- (AChE) and butyrylcholinestarase (BChE). Some (like Terminaline, Hookerianamide I, Chonemorphine, etc.) of them were interestingly found to be quite selective towards the BChE over AChE. For the docking calculations ICMTM docking module and for the study of the intermolecular interactions the program LigPlot have been used. During the docking studies the compounds showed good correlations with the in vitro activity profiles (IC50 values) and the docking (Edocking) and calculated binding energies (ΔG). When docked into AChE the correlation coefficient (R2) 0.808 and 0.813, respectively and when docked into BChE the R2 values were found to be 0.873 and 0.768, respectively. These correlations revealed remarkable agreements of the docking studies with the activity found from in vitro experiments. Majority and the large part of the compounds exhibited hydrogen bonds as well as hydrophobic interactions at the peripheral anionic subsite (PAS), which is at the entrance of the gorge. A number of compounds exhibited interesting interactions both the PAS and acyl-binding sites.

Keywords: Acetylcholinesterase, butyrylcholinestarase, cognition, docking, binding energy, ICM, LigPlot.

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2013
Page: [416 - 428]
Pages: 13
DOI: 10.2174/1574893611308040004
Price: $58