Synthesis Of Alkoxy-Isoflavones As Potential α-Glucosidase Inhibitors

Abstract The aim of the present study was to synthesize isoflavone-enaminones 3a-c and 7-alkoxy-isoflavones 4a-c, evaluate their inhibition of a-glucosidase, and analyze the bioisosteric effect of the presence versus absence of aromatic moieties in these benzopyran derivatives. All the test compounds exhibited a greater inhibition of a-glucosidase than the positive control acarbose. The series of isoflavones 3a-c and 4a-c showed a higher inhibitory activity (IC50 = 6.3 - 87.6 µM) than the parental 7-hydroxyisoflavones 2a-c (IC50 = 109.4 - 173.2 µM), suggesting that the attachment of a 4’-chloroacetophenone moiety to the 7-hydroxyl group of 2a-c is an efficient way to increase the inhibition of a-glucosidase. Furthermore, the aromatic moieties of the series of compounds 3 and 4 enhance the inhibitory activity by hydrophobic effects according to docking calculations.