title: Insights into the permeability of drugs and drug-like molecules from MI-QSAR and HQSAR studies.
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.
authors.affiliation: Centre for Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Ranajit N
authors.initials: RN
authors.lastname: Shinde
authors.forename: K
authors.initials: K
authors.lastname: Srikanth
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sobhia
mesh_terms: D002463:Cell Membrane Permeability; D006801:Humans; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010599:Pharmacokinetics; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations