Total Synthesis and Structure-Activity Relationships Study of Odilorhabdins, a New Class of Peptides Showing Potent Antibacterial Activity

被引：24

作者：

Sarciaux, Matthieu ^{[1
]}

Pantel, Lucile ^{[1
]}

Midrier, Camille ^{[2
]}

Serri, Marine ^{[1
]}

Gerber, Cristelle ^{[1
]}

de Figueiredo, Renata Marcia ^{[2
]}

Campagne, Jean-Marc ^{[2
]}

Villain-Guillot, Philippe ^{[1
]}

Gualtieri, Maxime ^{[1
]}

Racine, Emilie ^{[1
]}

机构：

[1] Nosopharm, 110 Allee Charles Babbage,Espace Innovat 2, F-30000 Nimes, France

[2] Univ Montpellier, CNRS, ENSCM Ecole Natl Super Chim, UMR 5253,ICGM, 8 Rue Ecole Normale, F-34296 Montpellier 5, France

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 17期

关键词：

L-THREONINE ALDOLASE; DRUG DISCOVERY; AMINO-ACID; NATURAL-PRODUCTS; RESISTANCE; DERIVATIVES; REAGENT; HEXAFLUOROPHOSPHATE; ENTEROBACTERIACEAE; ANTIBIOTICS;

D O I：

10.1021/acs.jmedchem.8b00790

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The spread of antibiotic-resistant pathogens is a growing concern, and new families of antibacterials are desperately needed. Odilorhabdins are a new class of antibacterial compounds that bind to the bacterial ribosome and kill bacteria through inhibition of the translation. NOSO-95C, one of the first member of this family, was synthesized for the first time, and then a structure-activity relationships study was performed to understand which groups are important for antibacterial activity and for inhibition of the bacterial translation. Based on this study an analogue showing improved properties compared to the parent compound was identified and showed promising in vitro and in vivo efficacy against Enterobacteriaceae.

引用

页码：7814 / 7826

页数：13

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