Design, Synthesis, and Biophysical Studies of Novel 1,2,3-Triazole-Based Quinoline and Coumarin Compounds

Abstract

A novel triazole-coumarin compound 2-oxo-N-((1-(6-oxo-6-(p-tolylamino)hexyl)-1H-1,2,3-triazol-4-yl)methyl)-2H-chromene-3-carboxamide (compound 6) and quinoline compound N-((1-(6-oxo-6-(p-tolylamino)hexyl)-1H-1,2,3-triazol-4-yl)methyl)quinoline-6-carboxamide (compound 9) are designed and synthesized using Cu(I)-catalyzed cycloaddition of alkyne and azide reaction. The binding interaction of coumarin and quinoline compounds with bovine serum albumin and human serum albumin has been explored using different photophysical studies. To determine the feasible binding sites and change in the microenvironment of the binding sites of the tryptophan (Trp)/tyrosine (Tyr) of the serum albumins exploiting Trp/Tyr emission in proteins, steady state and time-resolved fluorescence at room temperature (298 K) and low-temperature phosphorescence studies at 77 K have been carried out. The fluorescence spectroscopic study of Trp residue in both complexes showed that the strong quenching with the blue shift of the emission peak occurs through static quenching mechanism. The thermodynamic parameters obtained from isothermal titration calorimetry study clearly established the involvement of van der Waals force and hydrogen bonds during complexation. Molecular docking studies further predict the experimental findings of the protein-quinoline and coumarin complexes.