A method for rapid screening of interactions of pharmacologically active compounds with albumin.

A method for rapid screening of interactions of pharmacologically active compounds with albumin.
Anal Chim Acta. 2015 Jan 15;855:51-9
Authors: Majcher A, Lewandrowska A, Herold F, Stefanowicz J, Słowiński T, Mazurek AP, Wieczorek SA, Hołyst R
Abstract
We determine the association constants for ligand-protein complex formation using the flow injection method. We carry out the measurements at high flow rates (F=1mLmin(-1)) of a carrier phase. Therefore, determination of the association constant takes only a few minutes. Injection of 1nM of the ligand (10μL of 1μM concentration of the ligand solution) is sufficient for a single measurement. This method is tested and verified for a number of complexes of selected drugs (cefaclor, etodolac, sulindac) with albumin (BSA). We obtain K=4.45×10(3)M(-1) for cefaclor, K=1.00×10(5)M(-1) for etodolac and K=1.03×10(5)M(-1) for sulindac in agreement with the literature data. We also determine the association constants of 20 newly synthesized 3β- and 3α-aminotropane derivatives with potential antipsychotic activity - ligands of 5-HT1A, 5-HT2A and D2 receptors with the albumin. Results of the studies reported here indicate that potential antipsychotic drugs bind weakly to the transporter protein (BSA) with K≈10(2)-10(3)M(-1). Our method allows measuring K in a wide range of values (10(2)-10(9)M(-1)). This range depends only on the solubility of the ligand and sensitivity of the detector.
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Source: Analytica Chimica Acta - January 2, 2015 Category: Chemistry Authors: Majcher A, Lewandrowska A, Herold F, Stefanowicz J, Słowiński T, Mazurek AP, Wieczorek SA, Hołyst R Tags: Anal Chim Acta Source Type: research