Antioxidant and glycohydrolase inhibitory behavior of curcumin-based compounds: Synthesis and evaluation of anti-diabetic properties in vitro.

Naturally occurring anti-diabetic compound curcumin can prevent diabetes complications due to antioxidant and anti-inflammatory properties as well as the attenuation of postprandial hyperglycemia. In this line, we have synthesized thirteen curcumin based derivatives (L1-L13) by multi-component reaction, characterized by IR, 1HNMR, 13C NMR, MS, elemental analysis and evaluated for possible antioxidant properties and α-glucosidase (α-Glu) and α-amylase (α-Amy) inhibitory potential. The curcumin-based pyrano[2,3-d]pyrimidine derivatives could inhibit α-Glu and α-Amy enzyme activity which showed desirable antioxidant activity. Furthermore, among the series, L5, L12, L9, L10, L8 and L11 were identified as more potent inhibitors of α-Glu enzyme than curcumin and the compounds of L12, L4, L9, L5, L10, L8, L13, and L11 were the stronger inhibitors of the α-Amy enzyme in vitro. Besides, among them, L12 had the lowest IC50 for the inhibition of both enzymes. Since strong inhibitors for pancreatic α-Amy result in the progression of severe gastrointestinal side effects, the inhibitors that show the lower α-Amy/α-Glu inhibitory ratio have attracted much attention in medicinal chemistry. Besides, considering antioxidant characteristics of synthesized compounds, the L7 derivative with the highest antioxidant activity and the lowest "α-Amy/α-Glu inhibitory" ratio could be an appropriate candidate for further study through the rational drug design to the exploration of a new class of powerful anti-diabetic drugs.