Diverse phloroglucinols with hAChE inhibitory and anti-VRE effects from Rhodomyrtus tomentosa fruits

Rhodomyrtus tomentosa fruits serve as both functional food and medicinal resources due to their rich bioactive constituents and manifold pharmacological effects. Phytochemical exploration of the R. tomentosa fruits led to the identification of eight new polymethylated phloroglucinols, designated as rhodotomentodione F (1) and rhodotomentodimers H‒N (2‒8), along with six previously described congeners (9‒14). Based on the detailed inspection of comprehensive spectroscopic data, electronic circular dichroism (ECD) simulations, and nuclear magnetic resonance (NMR) calculations, and DP4+ analyses, the structures of phloroglucinols 1‒8 were determined. Heterodimeric phloroglucinols 3‒14 exhibited human acetylcholinesterase (hAChE) inhibitory activities, with 13 exhibiting the highest potency (IC₅₀ = 1.04 μM). Moreover, molecular docking analysis clarified the potential binding interactions between the most active phloroglucinol 13 with hAChE. In addition, phloroglucinols 11 and 12 displayed significant anti-VRE (vancomycin-resistant Enterococci) activities, with MIC values reaching as low as 1 μg/mL.