The synthesis of Schiff base derivatives of 3-aminobenzofuran-2-carboxamide, characterize them spectroscopically, and explain the mechanism of ligand-protein interaction. The interaction's primary driving factors were van der Waals, hydrophobic, and hydrogen bonding forces. Moreover, ligands have a high affinity for HSA at Sudlow site I through hydrophobic contact, hydrogen bonding, and groove binding to DNA, according to molecular docking investigations. DFT studies determined their FMOs and molecular parameters.

Abstract

The 1:1 M condensation of 3-aminobenzofuran-2-carboxamide, terephthalaldehyde and aniline produced eight novel Schiff base derivatives, which were then characterized via ¹H, and ¹³C NMR, FT-IR, and HRMS spectroscopic techniques. The synthesized compounds' biological potency was comprehensively assessed using HSA and DNA binding evaluations. Furthermore, fluorescence quenching, absorption spectroscopy, molecular docking, and DFT techniques were used to examine the binding of these Schiff base ligands to DNA/HSA. It is possible to deduce from the data analysis that the ATA6 ligands have the highest binding affinity to DNA/HSA. A groove-binding mechanism of DNA and van der Waals and Hydrogen bond of HSA interaction was explored for the synthesized compounds. Their specific DNA/HSA-binding was shown using molecular docking. This work is significant since it is the first comprehensive report on the in-depth theoretical and biological investigation of these substances.