New chalcone derivatives as potential inhibitors of bacterial efflux pumps in multidrug-resistant Staphylococcus aureus

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F25%3A43932648" target="_blank" >RIV/60461373:22330/25:43932648 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

New chalcone derivatives as potential inhibitors of bacterial efflux pumps in multidrug-resistant Staphylococcus aureus

Popis výsledku v původním jazyce

The alarming rise of multidrug-resistant bacteria due to the overuse of antibiotics in human and veterinary medicine poses a critical challenge to global public health. Methicillin-resistant Staphylococcus aureus (MRSA) exemplifies this problem, with resistance not only to methicillin but also to fluoroquinolones, macrolides, and cephalosporins. A key factor in MRSA resistance is the activity of bacterial efflux pumps, which actively expel antibiotics and contribute to treatment failures. Natural compounds offer a promising avenue for discovering new therapeutic agents, particularly those that act as adjuvants by targeting resistance mechanisms such as efflux pumps. Chalcones, widely found in traditional medicine, have emerged as potential candidates because of their structural versatility and biological activity. In our study, a library of 60 chalcone derivatives was screened for activity against MDR S. aureus. Several derivatives restored ciprofloxacin susceptibility in resistant strains, suggesting a mechanism involving efflux pump inhibition. Using a semi-automated ethidium bromide efflux assay, we demonstrated the potential of these compounds to inhibit bacterial efflux systems. On the basis of these findings, new chalcone derivatives were designed and synthesized and their functional mechanisms were further characterized. Our results highlight the potential of chalcones as a structural basis for the development of efflux pump inhibitors. These findings contribute to the larger effort to overcome antibiotic resistance by targeting one of its fundamental mechanisms.

Název v anglickém jazyce

New chalcone derivatives as potential inhibitors of bacterial efflux pumps in multidrug-resistant Staphylococcus aureus

Popis výsledku anglicky

The alarming rise of multidrug-resistant bacteria due to the overuse of antibiotics in human and veterinary medicine poses a critical challenge to global public health. Methicillin-resistant Staphylococcus aureus (MRSA) exemplifies this problem, with resistance not only to methicillin but also to fluoroquinolones, macrolides, and cephalosporins. A key factor in MRSA resistance is the activity of bacterial efflux pumps, which actively expel antibiotics and contribute to treatment failures. Natural compounds offer a promising avenue for discovering new therapeutic agents, particularly those that act as adjuvants by targeting resistance mechanisms such as efflux pumps. Chalcones, widely found in traditional medicine, have emerged as potential candidates because of their structural versatility and biological activity. In our study, a library of 60 chalcone derivatives was screened for activity against MDR S. aureus. Several derivatives restored ciprofloxacin susceptibility in resistant strains, suggesting a mechanism involving efflux pump inhibition. Using a semi-automated ethidium bromide efflux assay, we demonstrated the potential of these compounds to inhibit bacterial efflux systems. On the basis of these findings, new chalcone derivatives were designed and synthesized and their functional mechanisms were further characterized. Our results highlight the potential of chalcones as a structural basis for the development of efflux pump inhibitors. These findings contribute to the larger effort to overcome antibiotic resistance by targeting one of its fundamental mechanisms.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10606 - Microbiology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů