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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