title: 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.
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Afsoon
authors.initials: A
authors.lastname: Yousefi
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran. Electronic address: ryousefi@shirazu.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Yousefi
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Panahi
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Sarikhani
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran.
authors.forename: Amin Reza
authors.initials: AR
authors.lastname: Zolghadr
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Aminollah
authors.initials: A
authors.lastname: Bahaoddini
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran. Electronic address: khalafi@chem.susc.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Khalafi-Nezhad
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species; D000516:alpha-Amylases / Q000378:metabolism*; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D000516:alpha-Amylases; D000520:alpha-Glucosidases; D003474:Curcumin; C030986:pyrimidine
keywords: Anti-diabetic compounds; Curcumin; Multi-component reaction; Reactive oxygen species; α-Glucosidase