Open AccesscΔlog kwIAM: can we afford estimation of small molecules’ blood-brain barrier passage based upon in silico phospholipophilicity?
Author(s) -
Lucia Grumetto,
Giacomo Russo
Publication year - 2021
Publication title -
admet and dmpk
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.309
H-Index - 13
ISSN - 1848-7718
DOI - 10.5599/admet.1034
Subject(s) - in silico , lipophilicity , chemistry , linear regression , range (aeronautics) , mathematics , stereochemistry , statistics , materials science , biochemistry , gene , composite material
56 compounds, whose log BB values were known from the scientific literature, were considered and their phospholipophilicity values were calculated in silico. These values, along with either experimentally determined or calculated lipophilicity values, were used to extract cΔ/Δ’log kwIAM parameters. cΔ/Δ’log kwIAM values were found inversely related to data of blood-brain barrier passage, especially in the < -0.20 log BB range and on the IAM.PC.DD2 phase (r2 = 0.79). In multiple linear regression, satisfactory statistic models (r2 (n-1) = 0.76), based on cD/D’log kwIAM.MG along with other in silico calculated descriptors, were achieved. This method brings the potential to be applied, along with other methodologies, to filter out solutes whose BBB permeation is foreseen to be substandard, thus allowing pharmaceutical companies/research institutes to focus on candidates that are more likely to concentrate in the brain.