Structurally diverse polycyclic polyprenylated acylphloroglucinols with promising antibacterial activity from the flowers of Mesua ferrea

A phytochemical re-investigation of the flowers of Mesua ferrea led to the isolation of twelve polycyclic polyprenylated acylphloroglucinols (PPAPs), including seven previously unreported congeners (1-7). Their structures were determined through comprehensive analysis of the 1D, 2D NMR spectroscopic data, HRESIMS and quantum chemical ECD calculations. Structurally, mesuaferroic acids M (1) and N (2) feature a rare amine functionality at C-20. Compounds 3-7 were identified as laxifloranone derivatives with varying oxidative modifications on the prenyl substituents attached at C-3, C-5 and C-7 on the bicyclic[3.3.1]nonane-2,4,9-trione core. Compounds 3 and 8 displayed promising antibacterial activity. Both exerted an MIC (minimal inhibitory concentration) value of 4 mg/mL against Staphylococcus aureus ATCC25923 and Proteus vulgaris CPCC160013. Preliminary mechanistic studies indicated that laxifloranone (8) does not affect cell membrane integrity of S. aureus, but markedly induces membrane leakage and inhibits biofilm formation. Overall, the findings not only expand the structural diversity of PPAPs in M. ferrea, but also highlight their potential as promising leads for the development of novel antibacterial drugs.