Structure-Based Discovery of Symmetric Disulfides from Garlic Extract as Quorum Sensing Inhibitors.

Microorganisms are the most common cause of food spoilage. is a common foodborne pathogen that causes food spoilage and poses a serious threat to food safety. As a crucial target in antitoxicity strategies, the quorum sensing (QS) system shows promising potential for further development. The garlic extract diallyl disulfide exhibits inhibitory activity against the QS system of , with disulfide bonds serving as the active component. However, the biological activity of other symmetric disulfides has not been investigated in this capacity. The study synthesized 39 disulfide bond-containing analogs and evaluated their activity as quorum sensing inhibitors (QSIs). The results showed that -hydroxyphenyl substitution can replace the allyl groups while maintaining strong biological activity. The virulence factors production was reduced by compound , with the strongest inhibitory effect being observed on elastase production. Synergistic inhibition was observed in the presence of antibiotics like ciprofloxacin and tobramycin. successfully inhibited infection in the larvae model. Primary mechanism studies using transcriptome, surface plasmon resonance and molecular docking suggested that inhibits the QS system by targeting the LasR protein. Thus, compound could be used in developing QSIs for the control of infections.