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.