%0 Journal Article %T Synthesis and evaluation of 1,3,4-oxadiazole derivatives for development as broad-spectrum antibiotics %+ Chemistry, Oncogenesis, Stress and Signaling (COSS) %+ Unité de Recherche Risques Microbiens (U2RM) %+ Institut de Génétique et Développement de Rennes (IGDR) %A Tresse, Cédric %A Radigue, Richard %A Gomes von Borowski, Rafael %A Thepaut, Marion %A Hanh Le, Hong %A Demay, Fanny %A Georgeault, Sylvie %A Dhalluin, Anne %A Trautwetter, Annie %A Ermel, Gwennola %A Blanco, Carlos %A van de Weghe, Pierre %A Jean, Mickael %A Giard, Jean-Christophe %A Gillet, Reynald %Z This work was supported by the Direction Générale de l’Armement (#ANR-14-ASTR-0001, France) and the Agence Nationale pour la Recherche under the frame of the Joint JPI-EC-AMR Project named “Ribotarget - Development of novel ribosome-targeting antibiotics” (SNF No. 40AR40_185777, Europe). %< avec comité de lecture %@ 0968-0896 %J Bioorganic and Medicinal Chemistry %I Elsevier %V 27 %N 21 %P 115097 %8 2019-11 %D 2019 %R 10.1016/j.bmc.2019.115097 %M 31540826 %K Oxadiazoles %K Antibiotics %K Ribosome %K Trans-translation %K tmRNA %Z Chemical Sciences/Medicinal Chemistry %Z Life Sciences [q-bio]/Pharmaceutical sciences/Medication %Z Life Sciences [q-bio]/Microbiology and Parasitology/BacteriologyJournal articles %X 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. %G English %2 https://univ-rennes.hal.science/hal-02304766/document %2 https://univ-rennes.hal.science/hal-02304766/file/Tresse-2019-Synthesis%20and%20evaluation%20HAL.pdf %L hal-02304766 %U https://univ-rennes.hal.science/hal-02304766 %~ INSERM %~ UNIV-RENNES1 %~ CNRS %~ IFR140 %~ FNCLCC %~ MARQUIS %~ IGDR %~ STATS-UR1 %~ IGDR-TR %~ OSS %~ COMUE-NORMANDIE %~ UR1-UFR-SVE %~ UR1-HAL %~ UR1-SDV %~ TEST-UR-CSS %~ UNIV-RENNES %~ UNICAEN %~ TEST-HALCNRS %~ ANR %~ UR1-BIO-SA