In vitro investigation of binding interactions between albumin–gliclazide model and typical hypotensive drugs

Abstract

Type 2 diabetes management usually requires polytherapy, which increases the risk of drug-to-drug interactions. Among the multiple diabetes comorbidities, hypertension is the most prevalent. This study aimed to investigate the binding interactions between the model protein, bovine albumin, and the hypoglycemic agent gliclazide (GLICL) in the presence of typical hypotensive drugs: quinapril hydrochloride (QUI), valsartan (VAL), furosemide (FUR), amlodipine besylate (AML), and atenolol (ATN). Spectroscopic techniques (fluorescence quenching, circular dichroism) and thermodynamic experiments were employed. The binding of the gliclazide to the albumin molecule was affected by the presence of an additional drug ligand, which was reflected by the reduced binding constant of the BSA–DRUG–GLICL system. This may indicate a possible GLICL displacement and its enhanced pharmacological effect, as manifested in clinical practice. The analysis of the thermodynamic parameters indicated the spontaneity of the reaction and emphasized the role of hydrogen bonding and van der Waals forces in these interactions. The secondary structure of the BSA remained almost unaffected.