BDDE-Inspired Chalcone Derivatives as New Antimicrobial Adjuvants
The effective response of antibiotics is threatened by the proliferation of micro-organisms 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 fo...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Medical Sciences Forum |
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| Online Access: | https://www.mdpi.com/2673-9992/14/1/68 |
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| author | Ana Jesus Fernando Durães Nikoletta Szemerédi Joana Freitas-Silva Paulo Martins Costa Eugénia Pinto Madalena Pinto Gabriella Spengler Emília Sousa Honorina Cidade |
| author_facet | Ana Jesus Fernando Durães Nikoletta Szemerédi Joana Freitas-Silva Paulo Martins Costa Eugénia Pinto Madalena Pinto Gabriella Spengler Emília Sousa Honorina Cidade |
| author_sort | Ana Jesus |
| collection | DOAJ |
| description | The effective response of antibiotics is threatened by the proliferation of micro-organisms 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 discovering 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 <i>Enterococcus faecalis</i> B3/101. Three compounds caused a four-fold decrease in the minimum inhibitory concentration (MIC) values of vancomycin against <i>E. faecalis</i>. 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 EP inhibition. |
| first_indexed | 2024-03-11T06:06:31Z |
| format | Article |
| id | doaj.art-c38fd0246cff49ce9111f0278e2027a8 |
| institution | Directory Open Access Journal |
| issn | 2673-9992 |
| language | English |
| last_indexed | 2024-03-11T06:06:31Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medical Sciences Forum |
| spelling | doaj.art-c38fd0246cff49ce9111f0278e2027a82023-11-17T12:57:43ZengMDPI AGMedical Sciences Forum2673-99922022-11-011416810.3390/ECMC2022-13650BDDE-Inspired Chalcone Derivatives as New Antimicrobial AdjuvantsAna Jesus0Fernando Durães1Nikoletta Szemerédi2Joana Freitas-Silva3Paulo Martins Costa4Eugénia Pinto5Madalena Pinto6Gabriella Spengler7Emília Sousa8Honorina Cidade9Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalLaboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, HungaryCIIMAR—Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, PortugalCIIMAR—Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, PortugalCIIMAR—Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, PortugalLaboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, HungaryLaboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalLaboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalThe effective response of antibiotics is threatened by the proliferation of micro-organisms 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 discovering 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 <i>Enterococcus faecalis</i> B3/101. Three compounds caused a four-fold decrease in the minimum inhibitory concentration (MIC) values of vancomycin against <i>E. faecalis</i>. 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 EP inhibition.https://www.mdpi.com/2673-9992/14/1/68antibiotic resistanceBDDEhalogenated chalcone derivativesantimicrobial activityEP inhibitors |
| spellingShingle | Ana Jesus Fernando Durães Nikoletta Szemerédi Joana Freitas-Silva Paulo Martins Costa Eugénia Pinto Madalena Pinto Gabriella Spengler Emília Sousa Honorina Cidade BDDE-Inspired Chalcone Derivatives as New Antimicrobial Adjuvants Medical Sciences Forum antibiotic resistance BDDE halogenated chalcone derivatives antimicrobial activity EP inhibitors |
| title | BDDE-Inspired Chalcone Derivatives as New Antimicrobial Adjuvants |
| title_full | BDDE-Inspired Chalcone Derivatives as New Antimicrobial Adjuvants |
| title_fullStr | BDDE-Inspired Chalcone Derivatives as New Antimicrobial Adjuvants |
| title_full_unstemmed | BDDE-Inspired Chalcone Derivatives as New Antimicrobial Adjuvants |
| title_short | BDDE-Inspired Chalcone Derivatives as New Antimicrobial Adjuvants |
| title_sort | bdde inspired chalcone derivatives as new antimicrobial adjuvants |
| topic | antibiotic resistance BDDE halogenated chalcone derivatives antimicrobial activity EP inhibitors |
| url | https://www.mdpi.com/2673-9992/14/1/68 |
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