Antibacterial N-Arylcinnamamides as Anti-inflammatory Agents ^†

A series of ring-substituted N-arylcinnamamides was prepared, characterized, and investigated for their antimicrobial efficacy in detail. Several of these derivatives showed strong activities, especially against Gram-positive bacteria and mycobacteria; they were able to increase the antibacterial activity of clinically used antibiotics with different mechanisms of actions. They were even able to inhibit the growth of staphylococcal biofilm and disrupted mature biofilm in concentrations close to MICs. It was found that the activity of the arylcinnamamides is bactericidal. No cytotoxic effect on human cells was observed for the most effective compounds [1,2]. Thus, the investigated cinnamamides may be considered as promising compounds for future research.

As derivatives of cinnamic acid are known for their anti-inflammatory and antioxidant effects [3,4], the cytotoxicity of the most effective compounds was tested on chondrocytes, and no inhibition of proliferation was found up to 100 µg/mL concentration. Thus, based on the concepts of polypharmacology, multifactorial diseases, and multitarget drugs and the abovementioned results, the compounds were investigated on their ability to inhibit cartilage damage caused by inflammation processes. This contribution is focused especially on the anti-inflammatory investigation of ring-substituted N-arylcinnamamides in relation to the induction of apoptosis and expression of pro- and anti-inflammatory markers. Structure–activity relationships and the supposed mechanism of action are discussed.