Comparative study of two antipsychotic drugs binding to human serum albumin: By multispectroscopic and molecular docking methods

• Comparative analysis of the affinity interaction between two typical antipsychotics and HSA. • Combined multispectral and electrochemical methods compared the binding intensity of their interactions. • The two antipsychotics caused significant perturbations to the structure of the HSA. • Molecular docking demonstrated the existence of multiple forces during the interaction. Psychiatric disorders are common diseases with a high prevalence. Currently, increasing focus on the treatment of psychiatric disorders has driven the development and investigation of antipsychotic drugs. In this paper, two classical antipsychotic drugs risperidone (RIP) and paliperidone (PIP) were selected as research subjects to explore their action mechanism with biological macromolecule human serum albumin (HSA). Combined UV spectroscopy and time-resolved fluorescence spectroscopy results showed that the quenching of HSA by RIP/PIP was a static process, and this result was further confirmed by temperature-dependent experiments, while hydrogen bonding, electrostatic forces and hydrophobic forces existed in the above process. Furthermore, synchronous fluorescence spectroscopy, three-dimensional fluorescence spectroscopy and circular dichroism (CD) spectroscopy experiments demonstrated the effect on HSA before and after the addition of RIP/PIP. Electrochemical experiments results determined that K a of HSA and RIP/PIP system was 1.52 × 10 4 M −1 –2.85 × 10 4 M −1 . According to the competition experiments and molecular docking indicating RIP/PIP bound to site I of HSA. Finally, these results provided reliable information for the development of antipsychotic drugs.