Please login first
BDDE-Inspired Chalcone Derivatives as new antimicrobial adjuvants
1, 2 , 1, 2 , 3 , 2, 4 , 2, 4 , 2, 5 , 1, 2 , 3 , * 1, 2 , * 1, 2
1  Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal;
2  CIIMAR—Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal;
3  Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary.
4  ICBAS—Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
5  Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal .
Academic Editor: Alfredo Berzal-Herranz


The effective response of antibiotics is threatened by the proliferation of microorganisms that manifest resistance mechanisms, leading to an increase of progressively untreatable infectious diseases around the world. One solution to this problem could lie in shifting the strategy from searching for new antibacterials to discover new compounds that potentiate the antimicrobial activity of current antibiotics, therefore reverting resistance, through the interference with several mechanisms, including biofilm formation and efflux pumps (EPs). Using bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) as a template, a macroalgae brominated bromophenol with antimicrobial activity, a series of 18 chalcone derivatives was prepared and evaluated for its antimicrobial activity and potential to fight antibiotic resistance. This includes seven chalcones, six dihydrochalcones and five diarylpropanes. Among them, two chalcones exhibited interesting antifungal activity and all compounds reversed resistance to vancomycin in the environmental isolate Enterococcus faecalis B3/101. Three compounds caused a four-fold decrease in the minimum inhibitory concentration (MIC) values of vancomycin against E. faecalis. All the dihydrochalcones and diarylpropanes displayed inhibition of EPs and biofilm formation in the tested multidrug resistant strain, suggesting that these compounds are EP inhibitors. Notably, dihydrochalcones and diarylpropanes did not show cytotoxicity in a mouse embryonic fibroblast cell line and they can potentially be regarded as hits for bacterial EPs inhibition.

Keywords: antibiotic resistance; BDDE; halogenated chalcone derivatives; antimicrobial activity; EPs inhibitors.