1,3-dithiolium flavonoids - New weapons to combat antibiotic
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).
amount - 600.000 lei (approx. 122,450
- Funding period - 24 months (26.10.2020 - 15.11.2022).
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
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.
|Marius Ştefan, PhD, Project coordinator, Microbiology||
|Lucian Mihail Bîrsa, PhD, Organic Chemistry|
|Marius Mihășan, PhD, Molecular Biology|
|Laura Sârbu, PhD, Organic Chemistry|
|Mihaela Savu, Microbiology|
|Cristina Veronica Moldovan, Microbiology|