Dimeric Acylphloroglucinol Derivatives with Anti-MRSA Activities from Chamelaucium uncinatum

Chamelauciumols A–I (1–9), nine undescribed dimeric acylphloroglucinol derivatives, were isolated from the aerial parts of Chamelaucium uncinatum. Structurally, compound 1 featured a new carbon skeleton characterized by an unprecedented prenyl-substituted methanodibenzo[b,f][1,5]dioxocin core. Compounds 2 and 3 represented new dimeric scaffolds, consisting of two methylated acylphloroglucinol derivatives linked via prenyl units. Compounds 4–9 were new phloroglucinol dimers with various linkage patterns. The structures and absolute configurations of these compounds were elucidated by comprehensive spectroscopic data, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculation. Besides, the antibacterial activities against Gram-positive and Gram-negative bacterial strains of the isolates were evaluated. Compounds 3 and 4 exhibited potent inhibitory effects against methicillin-resistant Staphylococcus aureus with minimum inhibitory concentration values ranging from 0.5 to 1 μg/mL. A preliminary study on the mechanism of action revealed that compounds 3 and 4 exerted anti-MRSA effects through disrupting bacterial cell membrane integrity. Additionally, compounds 3 and 4 also demonstrated remarkable antibiofilm activities.