Studies of the Novel Bioactive Acridine‐1,3‐thiazolidin‐4‐one Derivatives With Human Serum Albumin Using Fluorescence Spectroscopy and Molecular Modelling

In this study, we employ spectroscopic, thermodynamic and molecular docking approaches to identify the mechanism by which thiazolidinone derivatives 4a-4d bind with human serum albumin. It has been suggested that the affinity of the interaction of derivatives 4a-4d with HSA is within the optimal range necessary for the transportation and distribution of compounds within the organism. The binding constant values for the derivative/HSA complexes were found to be 0.03-5.87 × 10⁵ M^-1. Both ΔH⁰ and ΔS⁰ values were negative, which indicates that binding occurs mainly through van der Waals forces and hydrogen bonding. The negative values calculated for ΔG⁰ indicate that the binding of derivatives 4a-4d with HSA is a spontaneous process. Our study also reveals that derivatives 4a-4d bind to the subdomain IB (Site III) of HSA and that this binding alters the conformation and thermodynamic stability of HSA. Molecular docking simulations suggest that the main binding forces are van der Waals interactions, hydrophobic interactions and hydrogen bonds. The studied compounds showed weak DPPH-scavenging activity at all of the tested concentrations. The results suggest that compound 4b with a phenyl substituent at the nitrogen atom of the 1,3-thiazolidin-4-one moiety can be considered the most potent antioxidant in the series.