title: Prediction of Milk/Plasma Concentration Ratios of Drugs and Environmental Pollutants Using In Silico Tools: Classification and Regression Based QSARs and Pharmacophore Mapping.
abstract: A large set of 185 compounds with diverse molecular structures and different mechanisms of therapeutic actions was used to develop and validate statistically significant classification and regression based QSTR models for predicting partitioning of drugs/chemicals into breast milk. Pharmacophore mapping was also carried out which showed four important features required for lower risk of secretion into milk: (i) hydrophobic group (HYD), (ii) ring aromatic group (RA), (iii) negative ionizable (NegIon) and (iv) hydrogen bond donor (HBA). QSTR and pharmacophore models were rigorously validated internally as well as externally to check the possibilities of any chance correlation and judge the predictive potential of the models. Pharmacological distribution diagrams (PDDs) were used for the classification model as a visualizing technique for the identification and selection of chemicals with lower partitioning into milk. Our in silico models enable to identify the essential structural attributes and quantify the prime molecular pre-requisites which were chiefly responsible for secretion into milk. The developed models were also implemented to screen milk/plasma partitioning potential for a huge number DrugBank database (http://www.drugbank.ca/) compounds.
authors.affiliation: Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India phone: +91-98315 94140; fax: +91-33-2837 1078 http://sites.google.com/site/kunalroyindia.
authors.forename: Supratik
authors.initials: S
authors.lastname: Kar
authors.affiliation: Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India phone: +91-98315 94140; fax: +91-33-2837 1078 http://sites.google.com/site/kunalroyindia. kunalroy_in@yahoo.com, kroy@pharma.jdvu.ac.in.
authors.forename: Kunal
authors.initials: K
authors.lastname: Roy
keywords: In silico; LDA; Milk-plasma partitioning; Pharmacophore; QSAR; QSTR