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The Effect of Chalcones on the Main Sources of Reactive Species Production: Possible Therapeutic Implications in Diabetes Mellitus

Author(s):

Adelaide Sousa, Daniela Ribeiro, Eduarda Fernandes and Marisa Freitas*   Pages 1 - 45 ( 45 )

Abstract:


Diabetes mellitus (DM) is characterized by hyperglycemia, resulting from defects in insulin secretion, insulin action or both. There are several factors such as hyperlipidemia and oxidative stress (OS), namely the production of reactive oxygen/nitrogen species (ROS/RNS), that actively contribute to the development and worsening of DM. Chalcones, also termed as benzalacetophenone or benzylidene acetophenone, present a 1,3-diaryl-2-propen-1-one scaffold that has been shown to be highly promising in the development of new antioxidant compounds. Considering the potential interest of antioxidant therapy, the present review scrutinizes the role of the main sources of ROS/RNS production during DM. The modulatory effect of chalcones against nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, mitochondrial respiratory chain and nitric oxide synthase, is also thoroughly discussed, establishing, whenever possible, a structure-activity relationship (SAR). From the SAR analysis, it can be stated that the presence of catechol groups, hydroxyl and methoxyl substituents in the chalcones scaffold improves their modulatory activity against the main sources of ROS/RNS production in DM.

Keywords:

Chalcones, diabetes mellitus, oxidative stress, NADPH oxidase, xanthine oxidase, mitochondrial respiratory chain, nitric oxide synthase.

Affiliation:

LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical, Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical, Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical, Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical, Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto



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