Quorum-sensing Inhibitory Activity of Xanthones from Hypericum Curvisepalum N. Robson Against Chromobacterium...

In recent years, bacterial drug resistance has increased alarmingly. The scarcity of novel antibiotics and few available drug targets significantly contribute to rising drug resistance. Searching quorum-sensing interfering agents and biofilm formation inhibitors are the most promising approaches for fighting multi-drug resistant bacterial infections. Chinese herbal medicines represent a rich repository for discovering quorum sensing (QS) inhibitors. In a continuation of the search for QS inhibitors from plants of Hypericum, significant bioactivity was observed in the ethyl acetate extract of Hypericum curvisepalum. Twelve known xanthones were obtained from this extract through bioassay-guided fractionation and subsequent identification (1-12), together with an undescribed analogue (16), two chromone derivatives (13 and 14), and a flavonoid (15). Compounds 2, 3, 6, and 7 showed apparent anti-quorum sensing activity against Chromobacterium violaceum ATCC12472 with violacein inhibition rates of 91.2, 90.6, 88.3, and 83.0% at 250 μM. In addition, compounds 2, 3, 6, and 7 also suppressed the motility and significantly reduced the biofilm formation of C. violaceum ATCC12472. Molecular docking analyses, Isothermal titration calorimetry (ITC) and qRT-PCR experiments suggested that these four compounds could bind with CviR receptor and downregulated genes vioB, vioC, and vioD encoding to regulate violacein biosynthesis. Xanthones from Hypericum could be considered as an important source of natural QS inhibitors towards C. violaceum ATCC12472.