The present work proposes a novel application of EPSA (not an acronym but found to be referred to by many as Exposed Polar Surface Area), a supercritical fluid chromatography (SFC) polarity readout for assisting in the prediction of the extent of drug permeation through the blood-brain barrier (BBB). For this purpose, EPSA values for 69 structurally unrelated acidic, basic, neutral and amphoteric compounds were determined by a validated SFC method. Additionally, water-accessible surface area (WASA) values for the whole dataset were calculated in silico and compared to experimentally determined EPSA values. All these indexes were used to model the uptake of drugs through the BBB. Highly significant statistical models (r2 (n−1)=0.81) were achieved by using WASA and/or EPSA values along with other experimentally determined (e.g. phospholipophilicity) and in silico calculated descriptors.

Entry of therapeutics into the brain: Influence of exposed polarity calculated in silico and measured in vitro by supercritical fluid chromatography

Russo, Giacomo;Barbato, Francesco;Grumetto, Lucia;
2019

Abstract

The present work proposes a novel application of EPSA (not an acronym but found to be referred to by many as Exposed Polar Surface Area), a supercritical fluid chromatography (SFC) polarity readout for assisting in the prediction of the extent of drug permeation through the blood-brain barrier (BBB). For this purpose, EPSA values for 69 structurally unrelated acidic, basic, neutral and amphoteric compounds were determined by a validated SFC method. Additionally, water-accessible surface area (WASA) values for the whole dataset were calculated in silico and compared to experimentally determined EPSA values. All these indexes were used to model the uptake of drugs through the BBB. Highly significant statistical models (r2 (n−1)=0.81) were achieved by using WASA and/or EPSA values along with other experimentally determined (e.g. phospholipophilicity) and in silico calculated descriptors.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/753986
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