cΔlog kwIAM: can we afford estimation of small molecules’ blood-brain barrier passage based upon in silico phospholipophilicity?

  • Lucia Grumetto Pharm-Analysis & Bio-Pharm Laboratory, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano, 49, I-80131, Naples, Italy https://orcid.org/0000-0002-3529-1819
  • Giacomo Russo School of Applied Sciences, Sighthill Campus, Edinburgh Napier University, 9 Sighthill Ct, EH11 4BN Edinburgh, United Kingdom https://orcid.org/0000-0002-2964-389X
Blood-Brain Barrier passage of small molecules


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.


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