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Computational approaches to enhance activity of taxanes as antimitotic agent
Ponnurengan Malliappan Sivakumar,
Published in
2012
Volume: 21
   
Issue: 9
Pages: 2557 - 2570
Abstract
Eighty semisynthetic taxanes were used to develop a quantitative structure activity relationship (QSAR) and also dock with the microtubule assembly and develop a relationship between binding energy and activity. These two equations could be used to predict activity of new taxanes. The data collected from literature were divided into training (61) and test (19) sets and the former were used to develop the equation. In the QSAR, topological, hydrophobic, and structural descriptors are found to be the major contributors of activity. The statistical parameters r 2 (0.72), r 2 adj (0.69), q 2 (0.65), and F ratio (23.26) were found to be satisfactory and the predictions were with in the 99% confidence interval. The docking studies of taxanes (using training set compounds) using microtubule (PDB: 1JFF) shows that the binding energy is negatively correlated with the antimicrotubule activity (r = -0.66). Hydrogen bond is found to be predominant factor for the binding of the taxanes with the microtubule. The relationship between binding energy and activity (r 2 (0.72), r 2 adj (0.69), q 2 (0.65), and F ratio (23.26)) was able to predict the data in the test set within the 99% confidence limits. In addition, these theoretical studies will give additional inputs to the medicinal chemists to design newer and potent taxane derivatives as antimitotic agents. © Springer Science+Business Media, LLC 2011.
About the journal
JournalMedicinal Chemistry Research
ISSN10542523
Open AccessNo
Concepts (16)
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    Antimitotic agent
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    Taxane derivative
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    Article
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    Binding affinity
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    Confidence interval
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    Correlation analysis
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    Drug activity
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    Drug structure
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    Hydrogen bond
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    Hydrophobicity
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    Mathematical analysis
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    Microtubule
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    Microtubule assembly
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    Nonhuman
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    Quantitative structure activity relation
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    STATISTICAL PARAMETERS