Semisynthetic Vitamin E Derivatives as Potent Antibacterial Agents against Resistant Gram-Positive Pathogens.
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.
['Viault|Guillaume|G|0000-0002-7359-7595', 'Kempf|Marie|M|', 'Ville|Alexia|A|', 'Alsabil|Khaled|K|', 'Perrot|Rodolphe|R|', 'Richomme|Pascal|P|', 'Hélesbeux|Jean-Jacques|JJ|', 'Séraphin|Denis|D|']
D000900:Anti-Bacterial Agents D004305:Dose-Response Relationship, Drug D016106:Methicillin Resistance D008826:Microbial Sensitivity Tests D015394:Molecular Structure D013211:Staphylococcus aureus D013212:Staphylococcus epidermidis D013329:Structure-Activity Relationship D014810:Vitamin E
vitamin E antibacterial agents methicillin-resistant Staphylococcus aureus natural products semisynthesis