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

Grumetto, Lucia; Russo, Giacomo

Abstract

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 k w IAM parameters. cΔ/Δ'log k w IAM 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 (r 2 = 0.79). In multiple linear regression, satisfactory statistic models (r 2 (n-1) = 0.76), based on c/'log k w IAM.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.

Citation

Grumetto, L., & Russo, G. (2021). cΔlog kwIAM: can we afford estimation of small molecules’ blood-brain barrier passage based upon in silico phospholipophilicity?. ADMET and DMPK, 9(4), 267-281. https://doi.org/10.5599/admet.1034

• Journal Article Type: Article
• Acceptance Date: Nov 27, 2021
• Online Publication Date: Dec 15, 2021
• Publication Date: 2021
• Deposit Date: Dec 17, 2021
• Publicly Available Date: Dec 17, 2021
• Journal: ADMET and DMPK
• Print ISSN: 1848-7718
• Publisher: International Association of Physical Chemists
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 4
• Pages: 267-281
• DOI: https://doi.org/10.5599/admet.1034
• Keywords: immobilized artificial membrane; biochromatography; blood brain barrier; brain targeting; phospholipophilicity
• Public URL: http://researchrepository.napier.ac.uk/Output/2830552