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3D-QSAR and molecular docking studies of 4-anilinoquinazoline derivatives: a rational approach to anticancer drug design

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Abstract

The present article is an attempt to formulate the three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling of 4-anilinoquinazoline derivatives having promising anticancer activities inhibiting epidermal growth factor (EGFR) kinase. Molecular field analysis was applied for the generation of steric and electrostatic descriptors based on aligned structures. Partial least-squares (PLS) method was applied for QSAR model development considering training and test set approaches. The PLS models showed some interesting results in terms of internal and external predictability against EGFR kinase inhibition for such type of anilinoquinazoline derivatives. Steric and electrostatic field effects are discussed in the light of contribution plot generated. Finally, molecular docking analysis was carried out to better understand of the interactions between EGFR target and inhibitors in this series. Hydrophobic and hydrogen-bond interactions lead to identification of active binding sites of EGFR protein in the docked complex.

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Authors and Affiliations

  1. Structural Biology and Bioinformatics Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Calcutta, 700032, India

    Sisir Nandi & Manish C. Bagchi

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  1. Sisir Nandi
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  2. Manish C. Bagchi
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Correspondence to Manish C. Bagchi.

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Nandi, S., Bagchi, M.C. 3D-QSAR and molecular docking studies of 4-anilinoquinazoline derivatives: a rational approach to anticancer drug design. Mol Divers 14, 27–38 (2010). https://doi.org/10.1007/s11030-009-9137-9

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  • DOI: https://doi.org/10.1007/s11030-009-9137-9

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