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Insights into the permeability of drugs and drug-likemolecules from MI-QSAR and HQSAR studies

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Abstract

Membrane-interaction QSAR (MI-QSAR) and Holographic QSAR (HQSAR) analyses have been performed on a diverse set of drugs and drug-like molecules. MI-QSAR combines a set of membrane-solute interaction properties calculated during molecular dynamics simulation with the set of classical solute descriptors to predict the biological behavior of drugs and drug-like molecules. HQSAR is a technique which employs fragment fingerprints or molecular holograms as predictive variables of biological activity. A data set of 60 structurally diverse molecules with permeability coefficients were used to construct significant MI-QSAR and HQSAR models of Caco-2 cell permeation. A statistically meaningful MI-QSAR model was obtained with r 2 = 0.805 and q 2 = 0.696. Subsequently, HQSAR models were developed on the same data set. The best HQSAR model (r 2 = 0.915, q 2 = 0.539) was obtained with fragment distinctions atom, bond, donor and acceptor with atom count 4 to 7. The predictions for training and test set molecules are in good agreement with experimental results and show the potential of models for untested compounds. This displays the importance of MI-QSAR and HQSAR analysis in estimating ADME properties characterized by the transport of solutes through biological membranes.

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Acknowledgments

The authors thank Department of Science and Technology (DST), Delhi, and Council of Scientific and Industrial Research (CSIR), New Delhi for financial assistance.

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Authors and Affiliations

  1. Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, 160062, India

    Ranajit N. Shinde, K. Srikanth & M. Elizabeth Sobhia

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  1. Ranajit N. Shinde
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  2. K. Srikanth
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  3. M. Elizabeth Sobhia
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Correspondence to M. Elizabeth Sobhia.

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Shinde, R.N., Srikanth, K. & Sobhia, M.E. Insights into the permeability of drugs and drug-likemolecules from MI-QSAR and HQSAR studies. J Mol Model 18, 947–962 (2012). https://doi.org/10.1007/s00894-011-1121-5

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  • DOI: https://doi.org/10.1007/s00894-011-1121-5

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