Volume 78, July 2015, Pages 46–55
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.
Graphical abstract
Keywords
- α-Glucosidase;
- Anti-diabetic compounds;
- Curcumin;
- Reactive oxygen species;
- Multi-component reaction
Copyright © 2015 Elsevier B.V. All rights reserved.
