QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS ANALYSIS OF THE ANTICONVULSANT ACTIVITY OF ERYTHRININE
Abstract
ABSTRACT
Objective: The objective of this study is to determine the biological activity of Erythrinine against human nicotinic acetyl cholinergic receptor bquantitative structure-activity relationships (QSAR) and determine the anticonvulsant activity of the crude extract of Erythrina indica in mice.
Methods: Half minimal inhibitory concentration (IC50) of structurally similar analogs was identified from a literature. 298 2D and 3D descriptors
were computed using molecular operating environment. The compounds were divided into training set and test set after principal component
analysis. Multiple linear regression (MLR) analysis was carried out using International Business Machines - Statistical Package for the Social Sciences,
version 17 (IBM SPSS 17). Molecular docking analysis was carried out using Autodock 4.2. The in vitro anticonvulsant activity of the crude extract was
determined by administration of alcoholic extract to albino mice of either sex on pentylene tetrazole-induced seizures.
Results: Computed descriptors were used as independent variables. The model with high correlation coefficient was selected for the biological activity
of Erythrinine (r
=0.982). The biological activity of Erythrinine was found to be 0.62 µmol/L. Interactions of Erythrinine with the druggable domains of
human nicotinic acetyl cholinergic receptor was elucidated by molecular docking which showed a binding energy of −7.12 kcal/mol and IC50 5.95 µM.
When administered to the albino mouse of either sex, the crude extract offered significant protection of 71.4% against pentylenetetrazole-induced
convulsions.
2
Conclusion: The study has determined the antiepileptic activity of Erythrinine to act through a novel mechanism of nicotinic acetyl cholinergic
receptor inhibition (nAchR). Future studies have to be carried out to determine the activity of similar analogs and thereby identify molecules that act
through this novel mechanism.
Keywords: Erythrinine, Quantitative structure-activity relationships, Multiple linear regression, Anticonvulsant.
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