ABSTRACT Antibiotic resistance, which renders existing antibiotics ineffective against bacterial infections, is among the top‐most pressing global public health challenges. A promising strategy to combat bacterial infection without inducing the occurrence of drug resistance is by disrupting quorum sensing (QS)—a complex communication circuit that bacterial pathogens employ to regulate their virulence. Therefore, QS inhibitors have emerged in recent times as potential therapeutic agents against bacterial infections. S ‐Ribosylhomocysteinase (LuxS) is one particularly attractive target in the QS pathway, which synthesizes the signaling molecule that mediates interspecies bacterial communication called autoinducer‐2 (AI‐2). In this study, we used computational chemistry and drug discovery techniques, molecular docking, drug‐likeness, toxicity prediction studies, and interaction profiling to identify bioactive phytochemicals from Annona muricata plant extract as potential anti‐QS agents against LuxS. Screening a library of 123 natural acetogenins from A. muricata , we identified gigantetronenin and isoannonacin as promising LuxS inhibitors. The potential inhibitory activity of these compounds against LuxS suggests that they could be explored as QS inhibitors with broad‐spectrum activity against bacterial pathogens. These findings highlight the potential of gigantetronenin and isoannonacin as novel therapeutic candidates for combating bacterial infections through QS inhibition.
Adewusi et al. (Sat,) studied this question.