albumin - publications

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1. Eur J Pharm Sci. 2012 Jan 28. [Epub ahead of print]

5-Imino-1,2-4-thiadiazoles and quinazolines derivatives as glycogen synthase
kinase 3β (GSK-3β) and phosphodiesterase 7 (PDE7) inhibitors: Determination of
blood-brain barrier penetration and binding to human serum albumin.

Pérez DI, Pistolozzi M, Palomo V, Redondo M, Fortugno C, Gil C, Felix G, Martinez
A, Bertucci C.

Instituto de Quimica Medica-CSIC (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid,
Spain.

5-Imino-1,2,4-thiadiazoles and quinazolines derivatives as glycogen synthase
kinase 3β (GSK-3β) and Phosphodiesterase 7 (PDE7) inhibitors were characterized
for their ability to pass the blood-brain barrier (BBB) together with their human
serum albumin (HSA) binding using high-performance liquid affinity chromatography
(HPLAC) and circular dichroism (CD). To study the blood-brain barrier
penetration, a parallel artificial membrane permeability assay (PAMPA) using a
porcine brain lipid was employed. For the HPLAC investigation, HSA was previously
covalently immobilized to the silica matrix of the HPLC column. This HSA-based
column was used to characterize the high affinity binding sites of
5-imino-1,2,4-thiadiazoles and quinazolines derivatives to HSA. Displacement
experiments in the presence of increasing concentrations of competitors known to
bind selectively to the main binding sites of HSA were carried out to determine
their possible binding site. The same drug-protein system was studied by CD. The
analysed compounds were able to pass BBB, they present good drug-like properties
and they showed a high affinity to HSA. Competition experiments showed an
anticooperative interaction at sites I and II, and an independent binding at
bilirubin binding site on HSA.

Copyright © 2012 Elsevier B.V. All rights reserved.

PMID: 22306656 [PubMed - as supplied by publisher]