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  • 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.

Analytica chimica acta (2014-12-30)
Aldona Majcher, Anna Lewandrowska, Franciszek Herold, Jacek Stefanowicz, Tomasz Słowiński, Aleksander P Mazurek, Stefan A Wieczorek, Robert Hołyst
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=1 mL min(-1)) of a carrier phase. Therefore, determination of the association constant takes only a few minutes. Injection of 1 nM of the ligand (10 μL of 1 μM 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methylamine solution, 33 wt. % in absolute ethanol ((denatured with 1% toluene))
Sigma-Aldrich
Methylamine solution, 2.0 M in THF
Sigma-Aldrich
Sulindac, ≥98.0%
Sigma-Aldrich
Methylamine solution, 2.0 M in methanol
Sigma-Aldrich
Methylamine solution, 40 wt. % in H2O
Sulindac, European Pharmacopoeia (EP) Reference Standard
USP
Cefaclor, United States Pharmacopeia (USP) Reference Standard
Etodolac, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Cefaclor
Sigma-Aldrich
Etodolac
Supelco
Cefaclor, Pharmaceutical Secondary Standard; Certified Reference Material