A Novel Approach for the Identification of Selective Anticonvulsants Based on Differential Molecular Properties for TBPS Displacement and Anticonvulsant Activity: An Integrated QSAR Modelling
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
A Novel Approach for the Identification of Selective
Anticonvulsants Based on Differential Molecular Properties for
TBPS Displacement and Anticonvulsant Activity: An Integrated
QSAR Modelling
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| Creator |
Bhutoria, Savita
Ghoshal, Nanda |
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| Subject |
Structural Biology & Bioinformatics
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| Description |
In order to gain insight into the structural and molecular requirements influencing the
anticonvulsant activity against Pentylenetetrazole (PTZ)-induced seizures and [35S] tert-
Butyl-bicyclophosphorothionate (TBPS) displacement property (a measure of binding to
GABAA receptor), Quantitative Structure –Activity Relationship (QSAR) studies have
been performed on a series of congeneric anticonvulsant agents proposed to act by
binding to the lactone site of the GABAA receptor. The aim of this workwas to identify
and analyse the various functionalities, which determine the TBPS displacement property
and anticonvulsant activity by correlating with various molecular descriptors. Statistical
techniques like Principal Component Analysis (PCA), Partial Least Squares (PLS),
Multiple Linear Regression (MLR) and Genetic Function Approximation (GFA) were
applied to identify the structural and physicochemical requirements for TBPS
displacement property and anticonvulsant activity. The generated equations were statistically
validated using leave-one-out cross-validation technique and randomization. The
best models were also validated by prediction of activity of compounds, not used for the
development of QSAR models. The results from reasonably good QSAR models (statistically
validated) clearly indicated that TBPS displacement property and the anticonvulsant
activity are defined by different molecular parameters. Based on this finding, a
novel approach is proposed, using integrated QSAR modelling, for the identification of
potential and selective anticonvulsant agents.
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| Date |
2008
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/186/1/QSAR_%26_COMBINATORIAL_SCIENCE%2C27(7)%2C_876%2D889%2C2008[68].pdf
Bhutoria, Savita and Ghoshal, Nanda (2008) A Novel Approach for the Identification of Selective Anticonvulsants Based on Differential Molecular Properties for TBPS Displacement and Anticonvulsant Activity: An Integrated QSAR Modelling. QSAR Comb. Sci, 27 (7). pp. 876-889. |
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| Relation |
http://dx.doi.org/10.1002/qsar.200860001
http://www.eprints.iicb.res.in/186/ |
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