Chemical reactivity and biological activity of chalcones and other α,β-unsaturated carbonyl compounds

Abstract1. Chalcones are structural analogues of benzalacetophenone (BAP). Several derivatives have been identified in plants and anticarcinogenic and anti-inflammatory properties were attributed to the compounds, probably related to their direct antioxidant activity or stimulatory effects on the expression of endogenous defence enzymes like hemeoxygenase-1 (HO-1). HO-1 expression is triggered by the Nrf2-Keap1 signalling pathway, initiated by the addition of chalcones to thiol groups of Keap1 via Michael-type reaction.2. The present study used a model system estimating the reactivity of different synthetic chalcones and other α,β-unsaturated carbonyl compounds with thiols and compared the chemical reactivity with the biological activity, measured by HO-1 expression in human dermal fibroblasts.3. Chemical reactivity with the thiol group of N-acetylcysteine was determined with 5,5′-dithiobis-(2-nitrobenzoic acid) and followed chemical principles of structure–reactivity relationship. Most reactive were sulf...