Indole-based aryl sulfides target the cell wall of Staphylococcus aureus without detectable resistance.

Sulfur-containing classes of the scaffold "Arylthioindoles" have been evaluated for antibacterial activity; they demonstrated excellent potency against methicillin-resistant Staphylococcus aureus (MRSA) as well as against vancomycin-resistant strains and a panel of clinical isolates of resistant strains. In this study, we have elucidated the mechanism of action of lead compounds, wherein they target the cell wall of S. aureus. Further, S. aureus failed to develop resistance against two lead compounds tested in a serial passage experiment in the presence of the compounds over a period of 40 days. Both the compounds demonstrated comparable in vivo efficacy with vancomycin in a neutropenic mice thigh infection model. The results of these antibacterial activities emphasize the excellent potential of thioethers for developing novel antibiotics and may fill in as a target for the adjustment of accessible molecules to develop new powerful antibacterial agents with fewer side effects.