Preliminary study of the blood brain barrier penetration of some organic compounds and drugs

Partial Least Squares (PLS) regression of blood–brain permeation data (logBB) including 348 diverse organic compounds and drugs was built using 903 Dragon descriptors. The prediction performance of the obtained PLS model is acceptable: the squared correlation coefficient (cumulative sum of squares o...

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Bibliographic Details
Main Authors: Crisan Luminita
Pacureanu Liliana
Corporate Author: International Symposium on Analytical and Environmental Problems (21.) (2015) (Szeged)
Format: Book part
Published: 2015
Series:Proceedings of the International Symposium on Analytical and Environmental Problems 21
Kulcsszavak:Kémia
Online Access:http://acta.bibl.u-szeged.hu/55950
Description
Summary:Partial Least Squares (PLS) regression of blood–brain permeation data (logBB) including 348 diverse organic compounds and drugs was built using 903 Dragon descriptors. The prediction performance of the obtained PLS model is acceptable: the squared correlation coefficient (cumulative sum of squares of all the Y's explained by all extracted components) R 2 Y(CUM) = 0.822, the crossvalidated correlation coefficient (cumulative fraction of the total variation of the Y's that can be predicted by all the extracted components) Q 2 Y(CUM) = 0.640, the number of independent variables, X=487, for a dataset of 342 compounds (six compounds was outliers). The Y-randomization test demonstrated the absence of chance correlation which is confirmed by the lower values of regression line intercepts for R2 X(CUM) (0.307) and Q2 (CUM) (-0.320). The descriptors such as polar surface area (N,O and N,O,S,P polar contributions), octanol-water partition coefficient (Ghose-Crippen and Moriguchi), hydrophilic factor, complementary information content index and the number of H-bond donor atoms showed the largest Variables Importance in the Projection (VIP) values and can influence the logBB. The values of logBB predicted by our model display lower differences against experimental values of 342 compounds than logBB values predicted by QikProp.
Physical Description:149-154
ISBN:978-963-306-411-5