Synthesis of novel 2-thiohydantoin derivatives as potential anti-diabetic drugs

Abstract

Thiohydantoin is a hydantoin with one carbonyl group replaced with a thiocarbonyl group. In this study five series (glycinates, alaninates, butanoates, vallinates and norvalinates) of thiohydantoin derivatives (21a-v) were successfully synthesized and characterized using known analytical characterization techniques. The synthesis of these compounds followed four reaction steps using conventional methods from step one with nucleophilic substitution to Knoevenagel condensation reaction as the final step. All twenty two compounds were obtained in good to excellent yields and were subjected to in vitro screening for their inhibitory activity against α-glucosidase. Among the five series of thiohydantoin derivatives, the alaninate derivative 21f exhibited the highest inhibition at both concentrations of 65 μM and 130 μM, with values of 71.13±0.61 and 64.20±0.54, respectively. The glycinate derivative 21j exhibited the highest inhibition of 60.95±1.07 at 130 μM, while butanoate derivatives showed a consistant moderate inhibition. Only compound 21z exhibited concentration-dependent trends of moderate inhibition on the norvallinates derivatives and the vallinates exhibited negligible inhibition.