Investigating the interactions of benzoylaconine and benzoylhypacoitine with human serum albumin: Experimental studies and computer calculations

Benzoylaconine (BAC) and benzoylhypacoitine (BHA), which are derived from Aconitine (AC) and hypacoitine (HA), are commonly used in Traditional Chinese Medicine (TCM). The pharmacokinetics of drugs can be affected by their binding to proteins. Therefore, it is necessary to investigate drug-protein interactions. In this study, multi-spectroscopic, molecular docking and dynamics simulation were applied to investigate the interaction mechanisms of human serum albumin (HSA) with BAC/BHA. The binding constants (Ka) of the HSA-BAC/BHA systems at 298 K were 1.70 × 105 and 1.88 × 105 M−1, respectively. Stable HSA-BAC/BHA complexes were formed under the static quenching mode. Hydrogen bonds and van der Waals forces are the main driving forces during the spontaneous process, and BAC/BHA were suggested embedding into the site I of HSA. Circular dichroism (CD) spectroscopy revealed a reduction of 1.9% and 1.4% in the α-helical structure content of HSA induced by BAC/BHA. The molecular docking found that the electronic structure domains of the nitrogen and benzene ring skeletons were critical in the complex formation. Furthermore, computer simulations provided insights into the stability changes and illustrated that the residues such as TRP-214, LEU-219, and LEU-238 acted as key residues in the binding process between aconitine analogs and HSA.