@article{APS3593,
author = {Xiao-lei MA and Cheng CHEN and Jie YANG},
title = {Predictive model of blood-brain barrier penetration of organic compounds},
journal = {Acta Pharmacologica Sinica},
volume = {26},
number = {4},
year = {2016},
keywords = {},
abstract = {Aim: To build up a theoretical model of organic compounds for the prediction of
the activity of small molecules through the blood-brain barrier (BBB) in drug
design. Methods: A training set of 37 structurally diverse compounds was used to
construct quantitative structure-activity relationship (QSAR) models. Intermolecular
and intramolecular solute descriptors were calculated using molecular
mechanics, molecular dynamics simulations, quantum chemistry and so on. The
QSAR models were optimized using multidimensional linear regression fitting and
stepwise method. A test set of 8 compounds was evaluated using the models as
part of a validation process. Results: Significant QSAR models (R=0.955, s=0.232)
of the BBB penetration of organic compounds were constructed. BBB penetration
was found to depend upon the polar surface area, the octanol/water partition
coefficient, Balaban Index, the strength of a small molecule to combine with the
membrane-water complex, and the changeability of the structure of a solute-membrane-
water complex. Conclusion: The QSAR models indicate that the distribution
of organic molecules through BBB is not only influenced by organic solutes
themselves, but also relates to the properties of the solute-membrane-water complex,
that is, interactions of the molecule with the phospholipid-rich regions of cellular
membranes.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3593}
}