Tricyclic 1,3-dithiolium flavonoids - New weapons to combat antibiotic resistance
NR. 550PED ⁄ 2020

  • Research project funded by the Ministry of Education and Scientific Research - Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), PNCDI III - P2 - Increasing the competitiveness of the Romanian economy through RDI, Subprogramme 2.1 - Competitiveness through research, development and innovation).
  • Funding amount  - 600.000 lei (approx. 122,450 euro);
  • Funding period - 24 months (26.10.2020 - 15.11.2022).

Project summary:

    The discovery of penicillin followed by the use of antibiotics for the therapy of infectious diseases since the 1940s represented one of the most important moments in the evolution of modern medicine. However, a good number of pathogens have developed resistance to antibiotics, raising serious doubts about their efficiency in use. At present, antibiotic resistance of pathogenic microorganisms is a major concern of mankind, posing a serious threat to human health and economic development worldwide. The alarming spread of resistance along with the reduction of new developed antibiotics significantly decreased therapeutic possibilities, leading to increased mortality and morbidity. Finding effective new molecules to keep pace with antibiotic resistance is an important goal of current biomedical research.
In this context, the TriSflav project aimed to validate tricyclic synthetic flavonoids as effective antimicrobial agents. During the project, four flavonoids having I, Br, Cl and F as halogenated substituents at the benzopyran core were synthesized and characterized. The synthetic flavonoids were tested against bacterial (Staphylococcus aureus, Streptococcus pneumoniae, Acinetobacter baumannii, Enterococcus faecium and Escherichia coli, etc.) and fungal (Candida albicans, C. krusei and C. parapsilosis) clinically isolated strains, with different antibiotic resistance profiles. The obtained results showed that the tested synthetic flavonoids have important bactericidal and fungicidal properties, the antimicrobial activity being more important compared to antimicrobials such as penicillin, gentamicin or fluconazole. Antimicrobial effects are due to the fact that flavonoids target the cytoplasmic membrane, affecting its integrity and causing cell death. Furthermore, the proposed flavonoids influence some factors involved in antibiotic resistance or virulence. Thus, they show an important anti-biofilm activity, inhibiting the formation of biofilms or destroying mature microbial biofilms at low concentrations. The synthetic flavonoids have a reduced cytotoxicity at concentrations lower than 13.16 µg/ml and possess a pro-inflammatory effect.
Finally, the project proposed the flavonoid BrCl as an antimicrobial agent, with potential practical applications as an antibiotic and antiseptic (against some resistant strains of S. aureus, S. pneumoniae, A. baumannii and E. coli); disinfectant, against a wide spectrum of pathogenic microorganisms (including ESKAPE group pathogens and Candida species) resistant to antibiotics/antifungals.




Project members: 

Marius Ştefan, PhD, Project coordinator, Microbiology
Lucian Mihail Bîrsa, PhD, Organic Chemistry   
Marius Mihășan, PhD, Molecular Biology
Laura Sârbu, PhD, Organic Chemistry

PhD Students

Mihaela Savu, Microbiology
Cristina Veronica Moldovan, Microbiology

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