Dr Giacomo Russo G.Russo@napier.ac.uk
Lecturer
Determination of in Vitro and in Silico Indexes for the Modeling of Blood–Brain Barrier Partitioning of Drugs via Micellar and Immobilized Artificial Membrane Liquid Chromatography
Russo, Giacomo; Grumetto, Lucia; Szucs, Roman; Barbato, Francesco; Lynen, Frederic
Authors
Lucia Grumetto
Roman Szucs
Francesco Barbato
Frederic Lynen
Abstract
In the present work, 79 structurally unrelated analytes were taken into account and their chromatographic retention coefficients, measured by immobilized artificial membrane liquid chromatography (IAM-LC) and by micellar liquid chromatography (MLC) employing sodium dodecyl sulfate (SDS) as surfactant, were determined. Such indexes, along with topological and physicochemical parameters calculated in silico, were subsequently used for the development of blood–brain barrier passage-predictive statistical models using partial least-squares (PLS) regression. Highly significant relationships were observed either using IAM (r2 (n – 1) = 0.78) or MLC (r2 (n – 1) = 0.83) derived indexes along with in silico descriptors. This hybrid approach proved fast and effective in the development of highly predictive BBB passage oriented models, and therefore, it can be of interest for pharmaceutical industries as a high-throughput BBB penetration oriented screening method. Finally, it shed new light into the molecular mechanism involved in the BBB uptake of therapeutics.
Citation
Russo, G., Grumetto, L., Szucs, R., Barbato, F., & Lynen, F. (2017). Determination of in Vitro and in Silico Indexes for the Modeling of Blood–Brain Barrier Partitioning of Drugs via Micellar and Immobilized Artificial Membrane Liquid Chromatography. Journal of Medicinal Chemistry, 60(9), 3739-3754. https://doi.org/10.1021/acs.jmedchem.6b01811
Journal Article Type | Article |
---|---|
Online Publication Date | Apr 27, 2017 |
Publication Date | May 11, 2017 |
Deposit Date | Apr 29, 2020 |
Journal | Journal of Medicinal Chemistry |
Print ISSN | 0022-2623 |
Electronic ISSN | 1520-4804 |
Publisher | American Chemical Society |
Peer Reviewed | Peer Reviewed |
Volume | 60 |
Issue | 9 |
Pages | 3739-3754 |
DOI | https://doi.org/10.1021/acs.jmedchem.6b01811 |
Keywords | Sodium dodecyl sulfate, Peptides and proteins, Chromatography, Pharmaceuticals, Screening assays |
Public URL | http://researchrepository.napier.ac.uk/Output/2655682 |
You might also like
Downloadable Citations
About Edinburgh Napier Research Repository
Administrator e-mail: repository@napier.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2025
Advanced Search