Novel curcumin-based pyrano[2,3-d]pyrimidine anti-oxidant inhibitors for α-amylase and α-glucosidase: Implications for their pleiotropic effects against diabetes complications

Abstract

Curcumin (bis-α,β-unsaturated β-diketone), the chief constituent of turmeric plant (Curcuma longa), plays significant role in prevention of various diseases including diabetes. The research objective in the current study was to synthesize novel anti-diabetic curcumin derivatives with inhibitory properties against α-amylase (α-Amy) and α-glucosidase (α-Gls), as these two carbohydrate-hydrolysing enzymes are known to be important molecular targets for attenuation of postprandial hyperglycemia. The curcumin-based pyrano[2,3-d]pyrimidine derivatives were synthesized in the presence of curcumin, barbituric acids and aldehydes, using a multi-component reaction (MCR). Also, their inhibitory properties against α-Amy and α-Gls were evaluated spectroscopically. The curcumin-derived compounds with two invariant substructures (curcumin-based subunit and barbituric acid moiety) and one variable aryl (Ar) group demonstrated inhibitory action against α-Amy and α-Gls. Moreover, the synthetic compounds revealed prominent antioxidant activities, when examined by a 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) decolorization assay system. Overall, these antioxidant inhibitors are potentially important anti-diabetic drugs, not only to restore euglysemic condition, but also to limit activity of the major reactive oxygen species (ROS) producing pathways in diabetic patients.