Dimeric Acylphloroglucinol Derivatives with Anti-MRSA Activities from <i>Chamelaucium uncinatum</i>

Chamelauciumols A-I (<b>1</b>-<b>9</b>), nine undescribed dimeric acylphloroglucinol derivatives, were isolated from the aerial parts of <i>Chamelaucium uncinatum</i>. Structurally, compound <b>1</b> featured a new carbon skeleton characterized by an unprecedented prenyl-substituted methanodibenzo[<i>b</i>,<i>f</i>][1,5]dioxocin core. Compounds <b>2</b> and <b>3</b> represented new dimeric scaffolds, consisting of two methylated acylphloroglucinol derivatives linked via prenyl units. Compounds <b>4</b>-<b>9</b> 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 <b>3</b> and <b>4</b> exhibited potent inhibitory effects against methicillin-resistant <i>Staphylococcus aureus</i> with minimum inhibitory concentration values ranging from 0.5 to 1 μg/mL. A preliminary study on the mechanism of action revealed that compounds <b>3</b> and <b>4</b> exerted anti-MRSA effects through disrupting bacterial cell membrane integrity. Additionally, compounds <b>3</b> and <b>4</b> also demonstrated remarkable antibiofilm activities.