Synthesis and biological evaluation of oleanolic acid derivative-chalcone conjugates as alpha-glucosidase inhibitors

alpha-Glucosidase is a promising target for the treatment of obesity and diabetes mellitus. A series of oleanolic acid derivative-chalcone conjugates were designed and synthesized as alpha-glucosidase inhibitors. Their structures were determined by spectroscopic analysis and their alpha-glucosidase inhibitory activities were investigated in vitro. Most conjugates exhibited moderate inhibitory activity against alpha-glucosidase; among them, conjugate 1b (IC50 = 3.2 + 0.2 mu M) possessed the strongest alpha-glucosidase inhibitory activity, and the preliminary structure-activity relationship showed that the furan or thiophene rings in the chalcone units of the conjugates had a tendency to enhance the activity. Lineweaver-Burk plot analysis demonstrated competitive inhibition of alpha-glucosidase activity by 1b, 6b, 5c and 4d; their inhibition constant (K-i) values were 16.6, 29.3, 14.6 and 20.6 mu M, respectively. The interaction forces between the conjugates and alpha-glucosidase were hydrogen bonding and van der Waals.