Synthesis and biological activity of a potent optically pure autoinducer-2 quorum sensing agonist

• Autor(a) principal: Ascenso, Osvaldo S.
• Data de Publicação: 2019
• Outros Autores: Torcato, Inês M., Miguel, Ana Sofia, Marques, João C., Xavier, Karina B., Ventura, M. Rita, Maycock, Christopher D.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.7/944
• topic: Anti-Bacterial Agents; Bacterial Proteins; Carrier Proteins; Escherichia coli; Escherichia coli Proteins; Pentanones; Quorum Sensing; Stereoisomerism; Vibrio

Quorum sensing (QS) regulates population-dependent bacterial behaviours, such as toxin production, biofilm formation and virulence. Autoinducer-2 (AI-2) is to date the only signalling molecule known to foster inter-species bacterial communication across distantly related bacterial species. In this work, the synthesis of pure enantiomers of C4-propoxy-HPD and C4-ethoxy-HPD, known AI-2 analogues, has been developed. The optimised synthesis is efficient, reproducible and short. The (4S) enantiomer of C4-propoxy-HPD was the most active compound being approximately twice as efficient as (4S)-DPD and ten-times more potent than the (4R) enantiomer. Additionally, the specificity of this analogue to bacteria with LuxP receptors makes it a good candidate for clinical applications, because it is not susceptible to scavenging by LsrB-containing bacteria that degrade the natural AI-2. All in all, this study provides a new brief and effective synthesis of isomerically pure analogues for QS modulation that include the most active AI-2 agonist described so far.