Synthesis, Biological Properties, and Molecular Docking Studies of Pyrazolopyridine and Isoxazolopyridine Derivatives

Pyrazolopyridine and isoxazolopyridine derivatives were synthesized in a one-pot procedure from indan-1,3-dione, aromatic aldehydes, and 1,3-dimethyl-1 H -pyrazol-5-amine or 5-amino-3-methylisoxazole in the presence of eco-friendly thiamine hydrochloride or phase transfer catalysts under sonication. Tetrabutylammonium bromide and tetraethylammonium tetrafluoroborate were found to be the most efficient catalysts, with 69–92% yields in short reaction times. The interaction of human serum albumin (HSA) with the synthesized pyrazolopyridine and isoxazolopyridine derivatives were studied by examining the fluorescence quenching once the compound-albumin complex is formed. The Stern-Volmer equation was used to evaluate the binding parameters. Compound 4g showed the highest fluorescence quenching efficiency. DFT and molecular docking studies were also carried out for the synthesized compounds. In our study, DFT-based calculations were used to investigate changes in electron density as visualized through counter maps, electrostatic potential surface maps, and frontier orbitals. PDB structures 3V03, 4OR0, and 8EC1, representing serum albumin transport proteins, were chosen for docking studies. Additionally, in silico investigations on the DNA/bovine serum albumin (BSA) binding activity of the compounds were conducted. The results exhibited that all the synthesized compounds inhibited different activities of the transferred albumin. Compound 4g exhibited the highest binding affinity towards 3V03 (A and B chains) with a binding energy of -8.50 kcal/mol.