Antibacterial Activity Against Multidrug-Resistant Staphylococcus aureus and in Silico Evaluation of MepA Efflux Pump by Cinnamaldehyde Chalcone

Phytochemical studies on Croton species have identified the presence of secondary metabolites responsible for a wide variety of pharmacological activities, among them antimicrobial activity. Research for new substances with antimicrobial activity derived from natural products can give a major contribution to human health worldwide by finding more efficient and fewer toxic formulas in the race against pathogenic microorganisms' resistance. Among bacterial pathogens, Staphylococcus aureus species, despite being present in the skin and nasal mucosa, can cause many infections and diseases. These opportunists reach debilitated people in hospitals and are challenging to treat. Here, we performed the structural characterization, determination of antibiotic activity, and MepA efflux pump inhibition potential against S. aureus of the chalcone (2E, 4E) -1- (2-hydroxy-3,4,6-trimethoxyphenyl)-5-phenylpenta-2,4-dien-1-one, derived from natural products 2-hydroxy-3,4,6-trimethoxyacetophenone isolated from Croton anisodontus and cinnamaldehyde. The chalcone was synthesized by the Claisen-Schmidt condensation. In addition, microbiological tests were performed to investigate the antibacterial activity, modulator potential, and efflux pump inhibition against the S. aureus multi-resistant strains. MIC values obtained to chalcone were not clinically relevant (MIC ≥ 1024 µg/mL). However, chalcone hampers the binding of the antibiotic to the binding site of the MepA efflux pump. It acts as a competitive inhibitor, being expelled from the bacteria in place of the antibiotic and potentiating ciprofloxacin's action against multidrug-resistant bacterial strains of K2068. Therefore, chalcone can be used as a base for substance design with antibiotic modifying activity.