Effects of synthetic tetronamides and methylated denigrins on bacterial quorum sensing and biofilm formation

Detrimental biofilms of bacterial pathogens cause chronic infections with a high-level tolerance to antibiotics. To identify new control agents, we synthesized and tested a total of 14 tetronamides (including 5 new compounds) and 6 denigrin intermediates on the model species Escherichia coli. At a c...

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Detalles Bibliográficos
Autores: Sweta Roy, Jaime Acosta, Milandip Karak, Isabela Ramirez-velez, Kohei Torikai, Dacheng Ren, Luiz Cláudio de Almeida Barbosa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Brasil
Institución:Universidade Federal de Minas Gerais (UFMG)
Repositorio:Repositório Institucional da UFMG
Idioma:inglés
OAI Identifier:oai:repositorio.ufmg.br:1843/80563
Acceso en línea:https://doi.org/10.1021/acsomega.3c01729
http://hdl.handle.net/1843/80563
Access Level:acceso abierto
Palabra clave:Biofilm inhibition
Tetronamides
Denigrins
Butenolide
Patologia
Bactéria
Bactérias patogênicas
Biologia
Descripción
Sumario:Detrimental biofilms of bacterial pathogens cause chronic infections with a high-level tolerance to antibiotics. To identify new control agents, we synthesized and tested a total of 14 tetronamides (including 5 new compounds) and 6 denigrin intermediates on the model species Escherichia coli. At a concentration of 50 μg/mL, two tetronamides and two methylated denigrins exhibited significant inhibitory effects against biofilm formation of E. coli RP437, e.g., by 60 and 94%, respectively. Structural analysis of the tested compounds revealed that p-methoxybenzylidene and p-methoxyphenethyl moieties of denigrins are important for biofilm inhibition, while the former group is also essential to the activity against quorum sensing (QS) via AI-2. Specifically, tetramethyldenigrin B has strong inhibitory effects against both E. coli biofilm formation and AI-2-mediated QS and thus provides a promising lead structure for designing better control agents. Consistently, tetramethyldenigrin B also showed inhibitory activity against biofilm formation of uropathogenic E. coli. Together, these findings provide new insights for the rational design of novel biofilm and QS inhibitors.