Chalcones are bioactive molecules of natural and synthetic sources, whose physicochemical properties, reactivity, and biological activities are well-known among the scientific community. However, there are many molecules strictly related to chalcones with significantly less recognition like bis-chalcones. Several studies indicated that bis-chalcones have advantages over chalcones in specific bioactivities like anti-inflammatory activity. This review article describes the chemical structure and chemical properties of bis-chalcones, as well as the methods reported in the literature for the synthesis of these compounds highlighting the most recent developments. Finally, the anti-inflammatory activity of bis-chalcones is described, emphasizing the active structures found in literature and their mechanisms of action.

The inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, is one of the major therapeutic strategies for the treatment of type 2 diabetes mellitus. Chalcones have been recognized for their multiple biological activities, including antidiabetic properties, through unclear mechanisms. In the present work, a panel of chalcones bearing hydroxy, methoxy, methyl, nitro, chloro, fluoro and bromo substituents were evaluated against α-amylase and α-glucosidase activities, most of them for the first time. The results showed that the substitution patterns and the type of substituents of chalcones influence their inhibitory activity. The presence of hydroxy groups at C-2′- and C-4′ of the A ring and at C-3 and C-4 of the B ring favors the intended effect. Chalcones holding nitro groups and chloro substituents, together with a hydroxy group in the chalcone scaffold, showed strong inhibition of the α-glucosidase activity. The present study provides related scaffolds that may serve as the basis for the design and synthesis of new structures in order to obtain the ideal antidiabetic chalcone.