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Sulfonium, an Underestimated Moiety for Structural Modification, Alters the Antibacterial Profile of Vancomycin Against Multidrug‐Resistant Bacteria
Author(s) -
Guan Dongliang,
Chen Feifei,
Qiu Yunguang,
Jiang Bofeng,
Gong Likun,
Lan Lefu,
Huang Wei
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201902210
Subject(s) - sulfonium , vancomycin , chemistry , moiety , in vivo , bacteria , microbiology and biotechnology , biology , stereochemistry , organic chemistry , staphylococcus aureus , salt (chemistry) , genetics
In the antibiotics arsenal, vancomycin is a last resort for the treatment of intractable infections. However, this situation is under threat because of the increasing appearance of vancomycin‐resistant bacteria (VRB). Herein, we report a series of novel vancomycin derivatives carrying a sulfonium moiety. The sulfonium–vancomycin derivatives exhibited enhanced antibacterial activity against VRB both in vitro and in vivo. These derivatives also exhibited activity against some Gram‐negative bacteria. The sulfonium modification enhanced the interaction of vancomycin with the bacterial cell membrane and disrupts membrane integrity. Furthermore, the in vivo pharmacokinetic profile, stability, and toxicity of these derivatives demonstrated good druggability of the sulfonium–vancomycin analogues. This work provides a promising strategy for combating drug‐resistant bacterial infection, and advances the knowledge on sulfonium derivatives for structural optimization and drug development.