Synthesis of coumarins as carbonic anhydrase ii and α-glucosidase inhibitors

Abstract

Coumarins have been occupied an important position in medicinal chemistry. In this research, umbelliferone derivatives were evaluated for inhibitory activity of two enzymes, namely carbonic anhydrase II (CA II) and α-glucosidase. First, ether, brominated ether and ester derivatives of umbelliferone were synthesized, characterized and tested for CA II inhibitory activity. However, the inhibition data could not be used to make the exact conclusion about structure-activity relationship owing to their unrepeatable results. For the second part, thirty-four derivatives of umbelliferone (ether, brominated ether, ester, sulfonamide and sulfonate derivatives) were synthesized and explored for anti-α-glucosidase activity. It was disclosed that anti-α-glucosidase activity was affected by hydrophobic effect. In addition, bromo substituent at position 3 of ether derivatives of umbelliferone and sulfonamide substituents could improve anti-α-glucosidase activity. Three new compounds 45, 65 and 70 demonstrated good inhibitory activities with IC50 of 68, 88, and 37 µM, respectively, which were better than that of a positive control, acarbose (IC50 94 µM).