Functionalized chalcones with basic functionalities have antibacterial activity against drug sensitive Staphylococcus aureus

A library of chalcones with basic functionalities were evaluated for antibacterial activity against drug sensitive strains of Staphylococcus aureus and Escherichia coli. The most active compounds were 2-52 and 2-57 (MIC 6.3 μM S. aureus). These compounds had no activity against E. coli (MIC > 100 μM). Both compounds were characterized by a ring A that was substituted with 2-hydroxy-4,6-dimethoxy-3-(1-methylpiperidin-4-yl) groups. The phenolic OH and 1-methylpiperidinyl groups were required for activity but the phenolic OH may play a more critical role. While the compounds were comparable to licochalcone A in terms of antibacterial activity, they caused less hemolysis of sheep erythrocytes at high concentrations (100 μM). It was noted that the structural requirements for limiting hemolytic activity were less stringent than those required for antibacterial activity. The present findings suggest that the chalcone framework is an attractive template for optimization to achieve better potency, lower toxicity and a wider spectrum of antibacterial activity.

Chalcones with phenolic OH and basic heterocyclic rings had antibacterial activities comparable to licochalcone A (MIC 6.3 μM S. aureus) and protected erythrocytes from hemolysis at 100 μM.Figure optionsDownload as PowerPoint slide