Semi-synthetic vitamin E derivatives as potent antibacterial agents against resistant Gram-positive pathogens.

New 5-substituted vitamin E derivatives were semi-synthesized 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) and structure-activity relationships (SAR) were discussed. As a result, it was shown that the presence of a carboxylic acid function at C-5 position and/or at the end of the side chain was crucial for the antibacterial activity. The bactericidal or bacteriostatic action of three compounds against MRSA and MRSE was confirmed in time-kill kinetics study and 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.