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Pharmacophore modeling, molecular docking, QSAR, and in silico ADMET studies of gallic acid derivatives for immunomodulatory activity

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Abstract

Immunomodulation refers to an alteration in the immune response due to the intrusion of foreign molecules into the body. In the present communication, QSAR and docking studies of gallic acid derivatives were performed in relation to their immunomodulatory activities. Screening through the use of a QSAR model suggested that the compounds G-4, G-7, G-9, G-10, G-12, and G-13 possess immunomodulatory activity. Activity was predicted using a statistical model developed by the forward stepwise multiple linear regression method. The correlation coefficient (r 2) and the prediction accuracy (rCV2) of the QSAR model were 0.99 and 0.96, respectively. The QSAR study indicated that chemical descriptors—dipole moment, steric energy, amide group count, λ max (UV-visible) and molar refractivity—are well correlated with activity, while decreases in the dipole moment, steric energy, and molar refractivity were negatively correlated. A molecular docking study showed that the compounds had high binding affinities for the INFα-2, IL-6, and IL-4 receptors. Binding site residues formed H-bonds with the designed gallic acid derivatives G-3, G-4, G-5, G-6, G-7, and G-10. Moreover, based on screening for oral bioavailability, in silico ADME, and toxicity risk assessment, we concluded that compound G-7 exhibits marked immunomodulatory activity, comparable to levamisole.

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Acknowledgments

We acknowledge the Council of Scientific and Industrial Research, New Delhi, for financial support through networking project (NWP-09) at the Central Institute of Medicinal and Aromatic Plants, Lucknow, India.

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Authors and Affiliations

  1. Metabolic and Structural Biology Department, Council of Scientific and Industrial Research, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, UP, India

    Dharmendra Kumar Yadav & Feroz Khan

  2. Analytical Chemistry Department, Council of Scientific and Industrial Research, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, UP, India

    Arvind Singh Negi

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  1. Dharmendra Kumar Yadav
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  2. Feroz Khan
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  3. Arvind Singh Negi
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Correspondence to Feroz Khan.

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Yadav, D.K., Khan, F. & Negi, A.S. Pharmacophore modeling, molecular docking, QSAR, and in silico ADMET studies of gallic acid derivatives for immunomodulatory activity. J Mol Model 18, 2513–2525 (2012). https://doi.org/10.1007/s00894-011-1265-3

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