Novel synthesis of dihydropyrimidines for α-glucosidase inhibition to treat type 2 diabetes: In vitro biological evaluation and in silico docking

Abstract

A convenient and efficient new method has been established for the synthesis of dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This method is applicable for various substituted aldehydes as well as urea and thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine derivatives (4d, 4j). The biological assay revealed that the majority of compounds synthesized displayed modest inhibitory activity against α-glucosidase at low micro-molar concentrations. Molecular docking studies were also performed on the most active compound, 4f (with IC 50 value 112.21 ± 0.97 μM), to show the enzyme - inhibitor interactions. © 2014 Elsevier Inc. All rights reserved.