Synthesis and evaluation of 1,3,4-oxadiazole derivatives for development as broad-spectrum antibiotics

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Tresse, Cédric | Radigue, Richard | Gomes von Borowski, Rafael | Thepaut, Marion | Hanh Le, Hong | Demay, Fanny | Georgeault, Sylvie | Dhalluin, Anne | Trautwetter, Annie | Ermel, Gwennola | Blanco, Carlos | van de Weghe, Pierre | Jean, Mickael | Giard, Jean-Christophe | Gillet, Reynald

Edité par CCSD ; Elsevier -

International audience. The reality and intensity of antibiotic resistance in pathogenic bacteria calls for the rapid development of new antimicrobial drugs. In bacteria, trans-translation is the primary quality control mechanism for rescuing ribosomes arrested during translation. Because trans-translation is absent in eukaryotes but necessary to avoid ribosomal stalling and therefore essential for bacterial survival, it is a promising target either for novel antibiotics or for improving the activities of the protein synthesis inhibitors already in use. Oxadiazole derivatives display strong bactericidal activity against a large number of bacteria, but their effects on trans-translation were recently questioned. In this work, a series of new 1,3,4-oxadiazole derivatives and analogs were synthesized and assessed for their efficiency as antimicrobial agents against a wide range of gram-positive and gram-negative pathogenic strains. Despite the strong antimicrobial activity observed in these molecules, it turns out that they do not target trans-translation in vivo, but they definitely act on other cellular pathways.

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