The spread of multidrug resistant bacteria has fueled the development of new antibiotics to combat bacterial infections. Disrupting the quorum sensing (QS) mechanism with biomolecules is a promising approach against bacterial infections. Plants used in Traditional Chinese Medicine (TCM) represent a valuable resource for the identification of QS inhibitors. In this study, the in vitro anti-QS activity of 50 TCM-derived phytochemicals against the biosensor Chromobacterium violaceum CV026 was tested. Among the 50 phytochemicals, 7-methoxycoumarin, flavone, batatasin III, resveratrol, psoralen, isopsoralen, and rhein inhibited violacein production and showed good QS inhibitory effects. Batatasin III was selected as the best QS inhibitor based on drug-likeness, physicochemical properties, toxicity, and bioactivity score prediction analyses using SwissADME, PreADMET, ProtoxII, and Molinspiration. At 30 μg/ mL, Batatasin III inhibited violacein production and biofilm formation in C. violaceum CV026 by more than 69% and 54% respectively without affecting bacterial growth. The in vitro cytotoxicity evaluation by MTT assay demonstrated that batatasin III reduced the viability of 3T3 mouse fibroblast cells to 60% at 100 μg/mL. Furthermore, molecular docking studies showed that batatasin III has strong binding interactions with the QS-associated proteins CViR, LasR, RhlR, PqsE, and PqsR. Molecular dynamic simulation studies showed that batatasin III has strong binding interactions with 3QP1, a structural variant of CViR protein. The binding free energy value of batatasin III-3QP1 complex was -146.295 ± 10.800 KJ/mol. Overall results suggested that batatasin III could serve as a lead molecule that could be developed into a potent QS inhibitor.Communicated by Ramaswamy H. Sarma.
- Batatasin III
- Traditional Chinese Medicine (TCM)
- dynamic simulation
- molecular docking
- quorum sensing