Synthesis, characterization and investigating the binding mechanism of novel coumarin derivatives with human serum albumin: Spectroscopic and computational approach

Two 4-hydroxycoumarin derivatives: (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino) -ethylidene) chromane-2,4-dione (L1) and (E)-3-(1-((3-hydroxy-4-methoxyphenyl)-amino)ethylidene) chromane-2,4-dione (L2), were prepared and structurally characterized by spectroscopic techniques in combination with the B3LYP-D3BJ theoretical method. The interactions between newly synthesized compounds and human serum albumin (HSA) were investigated under physiological conditions at 296,303, and 310 K by fluorescence and absorption spectroscopy, molecular docking, and molecular dynamic simulations. The results of absorption and fluorescence spectral analysis showed that ligands quenched HSA fluorescence through a static process. The corresponding thermodynamic parameters Delta H-0, Delta S-0, and Delta G(0) were calculated according to Van't Hoff's equation. The obtained results indicated that compounds bind spontaneously to HSA mainly by van der Waals's forces and through hydrogen bonds. Ligand-competitive displacement experiments, using known site-specific ligands for HSA's binding sites (I and II) suggest that ligands had a higher affinity for site I (subdomain IIA). The results of the computational analysis follow the experimental data, and the obtained results suggest that the investigated compounds show a good binding affinity according to the HSA receptor, which will be useful for future studies related to rational drug design. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

Two 4-hydroxycoumarin derivatives were synthesized and characterized in terms of their structure using spectroscopic techniques and theoretical methods. The results showed that these compounds exhibit good binding affinity with human serum albumin (HSA) through van der Waals' forces and hydrogen bonds. This study is important for future research in rational drug design.