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

• A series of dihydropyrimidines and oxy bridged pyrimidines are synthesized.
• This novel method avoids the use of any expensive metal catalysts.
• Most of the synthesized compounds have shown promising α-glucosidase activity.
• Compound 4f presented the highest inhibitory activity with IC50 value 112.21 ± 0.97.
• Molecular modeling demonstrated the binding pattern.

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 IC50 value 112.21 ± 0.97 μM), to show the enzyme – inhibitor interactions.

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