RESUMO
Bacterial quorum sensing (QS) and biofilm formation are promising targets for developing new therapies to treat chronic infections. Herein, we report the stereoselective synthesis of 18 new analogs of natural cadiolides. Among the new compounds, substances 8b, 8f, 8i, 9a, 9b and 9e completely inhibited the biofilm formation of Escherichia coli RP347 in vitro. In addition, compound 8b interfered acyl-homoserine lactone (AHL) mediated QS, while 9e interrupted the QS via autoinducer-2 (AI-2). Biological assays also revealed that synthetic intermediates alkynones are potent inhibitors of AI-2 and AHL-mediated QS. These results indicate that cadiolides and alkynones are good candidates for further structural modification for a new generation of more potent antimicrobial agents.
Assuntos
4-Butirolactona/farmacologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , 4-Butirolactona/síntese química , Antibacterianos/síntese química , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , EstereoisomerismoRESUMO
In 2008, the Programa Rede Farmácia de Minas (RFM, literally translated: 'Minas Gerais Pharmacy Network' program) was created as a strategy to expand access to medicines. Aim: Measure access to medicines in public pharmacies through comparison between municipalities that joined or not the RFM. Materials & methods: Cross-sectional, evaluative study, gathering information from a representative sample of the municipalities in Minas Gerais between July 2014 and May 2015. The Poisson regression results were obtained by calculating the prevalence ratios. Results: Adequate access to medicines in Minas Gerais was 69.9%, being 75.8% in municipalities with and 69.2% without the RFM. The municipalities with the RFM showed statistically higher percentages in the Availability, Adequacy/Accommodation, and Acceptability dimensions. Conclusion: RFM appears an efficient strategy for promoting access to medicines.