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

TL;DR

This study identifies new compounds in Rhodomyrtus tomentosa fruits that inhibit an enzyme linked to Alzheimer's and show strong antibacterial effects.

Contribution

The discovery of eight new phloroglucinol compounds with potent hAChE inhibition and anti-VRE activity is novel.

Findings

Compound 13 showed the highest hAChE inhibition with an IC50 of 1.04 μM.

Compounds 11 and 12 exhibited strong anti-VRE activity with MIC values as low as 1 μg/mL.

Molecular docking confirmed the binding interactions of compound 13 with hAChE.

Abstract

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.

The online version contains supplementary material available at 10.1007/s13659-025-00557-0.

Figures