Studies on the competitive binding of cleviprex and flavonoids to plasma protein by multi-spectroscopic methods: A prediction of food-drug interaction

Abstract

Cleviprex is a short-acting dihydropyridine calcium channel antagonist used as an antihypertensive drug. In this work, the binding characterization of cleviprex to human serum albumin (HSA) and the competitive binding to HSA between cleviprex and two flavonoids, baicalin and rutin, were studied using multi-spectroscopic techniques and molecular docking method. The fluorescence quenching of HSA by cleviprex was initiated by the formation of HSA-cleviprex complex, which was confirmed by UV–vis spectra measurements. The results of thermodynamic analysis and molecular docking revealed that the hydrophobic interactions and hydrogen bonding were the major acting forces in stabilizing HSA-cleviprex complex. The results of substitution experiments and molecular docking demonstrated that cleviprex was mainly situated within the site I of HSA. Baicalin and rutin could reduce the values of binding constant and enhance the values of binding distance of cleviprex binding to HSA because they bind to the same binding site. The results of synchronous fluorescence and CD spectra suggested that the binding reaction of cleviprex to HSA could give rise to the changes of protein conformation and the combined actions of cleviprex and flavonoids could cause further changes of HSA conformation. Consequently, the intakes of flavonoid-rich foods and beverages should be lessened under the treatment of cleviprex to avoid food-drug interactions.