Probing the interaction between levamlodipine and hemoglobin based on spectroscopic and molecular docking methods.

Abstract

In recent years, levamlodipine (LAML) has been widely used as a common drug for the treatment of hypertension. However, no reports exist that focus on the binding process of LAML with the transport proteins present in blood circulation. Here, several spectroscopy techniques, molecular docking and a molecular dynamics simulation were employed to comprehensively analyze the mechanism underlying the interaction between bovine hemoglobin (BHb) and LAML, as well as the effect of other drugs on the BHb-LAML system. The results indicated that a stable BHb-LAML complex was formed and that the binding site for LAML was located at β-37 tryptophan in the central cavity of BHb. Van der Waals force and hydrogen bonds played major roles in this binding process, and the number of binding sites (n) in the binary system was approximately equal to 1. Multiple spectroscopy experiments (FT-IR and three-dimensional fluorescence spectrometry) and a dynamics simulation revealed that LAML could induce a conformational in BHb and that the microenvironment of Trp/Tyr changed. Interestingly, the values of the binding constant between LAML and BHb significantly increased due to the effect of rofecoxib, propranolol and enalapril. Meanwhile, these drugs did not produce synergistic or negative synergistic effects on the LAML binding with BHb. These results provide new insight into the transport mechanisms for LAML in the human body.