Design and synthesis of ferulic acid-based aldose reductase inhibitors as hypoglycemic agents

Twelve ferulic acid–based derivatives containing urea groups were synthesized and characterized by elementary analytical, 1 H and 13 C nuclear magnetic resonance and electrospray ionization mass spectrometry spectra. Their hypoglycemic and aldose reductase inhibitory activities were evaluated, several of which showed hypoglycemic activities in vivo comparable with the positive drug glibenclamide. Furthermore, of the tested compounds, 7a and 7b displayed the most potent aldose reductase inhibitory activity in vitro, with an IC 50 of 0.55 and 3.88 μM, respectively. Docking simulation indicated compound 7a mainly interact with aldose reductase 2 via three hydrogen bonds with ARG268, SER263, SER210, and one π–π stacking interaction with TYR209.