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Semisynthetic Vitamin E Derivatives as Potent Antibacterial Agents against Resistant Gram‐Positive Pathogens
Author(s) -
Viault Guillaume,
Kempf Marie,
Ville Alexia,
Alsabil Khaled,
Perrot Rodolphe,
Richomme Pascal,
Hélesbeux JeanJacques,
Séraphin Denis
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000792
Subject(s) - antibacterial activity , staphylococcus epidermidis , staphylococcus aureus , microbiology and biotechnology , cytotoxicity , chemistry , antibacterial agent , bacteria , biochemistry , antibiotics , biology , in vitro , genetics
New 5‐substituted vitamin E derivatives were semisynthesized, and their antibacterial activity against human Gram‐positive and Gram‐negative pathogens was evaluated. Several vitamin E analogues were active against methicillin‐resistant Staphylococcus aureus (MRSA) and/or methicillin‐resistant Staphylococcus epidermidis (MRSE); structure‐activity relationships (SARs) are discussed. As a result, it is shown that the presence of a carboxylic acid function at the C‐5 position and/or at the end of the side chain is crucial for the antibacterial activity. The bactericidal or bacteriostatic action of three compounds against MRSA and MRSE was confirmed in a time‐kill kinetics study, and the cytotoxicity on human cells was evaluated. The preliminary mechanism study by confocal microscopy indicated that those vitamin E analogues led to bacterial cell death through membrane disruption.