Background: Pyrano[3,2-c]quinoline derivatives 6a–n were synthesized via simple
two-step reactions and evaluated for their in vitro α-glucosidase inhibitory activity.
Methods: Pyrano[3,2-c]quinoline derivatives 6a–n derivatives were prepared from a two-step reaction:
cycloaddition reaction between 1-naphthyl amine 1 and malonic acid 2 to obtain
benzo[h]quinoline-2(1H)-one 3 and reaction of 3 with aryl aldehydes 4 and Meldrum’s acid 5. The
anti- α-glucosidase activity and kinetic study of the synthesized compounds were evaluated using
α-glucosidase from Saccharomyces cerevisiae and p-nitrophenyl-a-D-glucopyranoside as substrate.
The α-glucosidase inhibitory activity of acarbose was evaluated as positive control.
Results: All of the synthesized compounds, except compounds 6i and 6n, showed more inhibitory
activity than the standard drug acarbose and were also found to be non-cytotoxic. Among the synthesized
6e displayed the highest α-glucosidase inhibitory activity (IC50 = 63.7 ± 0.5 µM). Kinetic study of
enzyme inhibition indicated that the most potent compound, 6e, is a non-competitive inhibitor of
α-glucosidase with a Ki value of 72 µM. Additionally, based on the Lipinski rule of 5, the
synthesized compounds were found to be potential orally active drugs.
Conclusion: Our results suggest that the synthesized compounds are promising candidates for
treating type 2 diabetes.