Qualitative and quantitative measures of drugs’ placenta permeability - A chromatographic and computational approach

Title : Qualitative and quantitative measures of drugs’ placenta permeability - A chromatographic and computational approach

Abstract:

Novel Quantitative Structure-Activity Relationship (QSAR) models of compounds’ placenta (PL) permeability expressed as their: i) log FM (fetus-to-mother blood concentration) values; ii) Clearance Index (CI); iii) binary PL1/0 (crossing/non-crossing; Yes/No) score were generated based on chromatographic and computational descriptors. Chromatographic data were collected using Micellar Liquid Chromatography; computational descriptors were calculated using SwissADME and Mordred software available freely on-line.  Suitable computational descriptors were selected using Partial Least Square (PLS) technique. Predictive models of compounds’ log FM and CI were generated using a number of statistical tools: Multiple Linear Regression, Boosted Trees, and Artificial Neural Networks. Binary (qualitative) models of compounds’ placenta permeability (Yes/No) were generated using Discriminant Function Analysis and Principal Component Analysis.  All models were validated using a test set of compounds that were not used for model building.  Compounds of interest include drugs and environmental pollutants, e.g. pesticides. 

Audience Take Away Notes:

• The ability of compounds to cross the placenta may be predicted using chromatographic and computational data
• No human or animal experiments are needed
• Proposed models are applicable to drugs and environmental contaminants (e.g. pesticides) alike

Biography:

Dr. Anna W. Sobańska studied Chemistry at the Technical University of Lodz, Poland and graduated as MSc in 1992. She then joined the research group of Prof. Jeremy Robertson at Dyson Perrins Laboratory, Oxford University, UK. She received her PhD degree in Organic Chemistry in 2007 at the same institution. She obtained the position of a Formulation Chemist in Cosmetic Factory Pollena-Ewa in Lodz, Poland. In 2005 she joined the Department of Analytical Chemistry, Medical University of Lodz, Poland. She has published several research articles in SCI(E) journals. She has recently become a Professor of the Medical University of Lodz.