Novel polyhydroquinoline Schiff’s base derivatives: synthesis, characterization, in vitro α-glucosidase inhibitory, and molecular docking studies

Abstract

Novel Schiff’s base hydrazone derivatives (1–24) based on polyhydroquinoline (PHQ) were synthesized in good to excellent yields via three step reactions. Compound 1 (starting material) was synthesized through one pot multi-component unsymmetrical Hantzsch reaction by refluxing a mixture of ethyl-2-(2-formylphenoxy)acetate, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent for 6–8 h. The obtained PHQ was then refluxed with hydrazine hydrate in the presence of absolute ethanol for 4–5 h. to get compound 2. Finally, the hydrazide was treated with various substituted aromatic/aliphatic aldehydes to afford the desired hydrazone Schiff’s bases (3–24). All the produced analogues were structurally deduced with the help of LC-HRESI-MS, 1H- and 13C-NMR spectroscopy. The obtained compounds were evaluated for their α-glucosidase activity, where twelve compounds (10, 14, 7, 9, 8, 17, 12, 19, 13, 15, 21, and 11) were found the most active at IC50 ranging between 5.26 and 25.17 µM, compared to acarbose, a standard α-glucosidase inhibitor with IC50 of 873.34 ± 1.67 µM. The best hit compounds were docked within the acarbose binding pocket of α-glucosidase and vetted for their binding affinities.