Polymethylated acylphloroglucinols from Rhodomyrtus tomentosa exert acetylcholinesterase inhibitory effects

Bioorg Chem. 2021 Feb:107:104519. doi: 10.1016/j.bioorg.2020.104519. Epub 2020 Nov 27.

Abstract

Chemical investigation of the twigs and leaves of Rhodomyrtus tomentosa led to the isolation and structural identification of a novel polymethylated phloroglucinol meroterpenoid (PPM) featuring a 6/6/6/6 tetracyclic system, rhotomentodione F (1), five new polymethylated polycyclic phloroglucinols (PPPs) with a rare bis-furan framework, rhotomentosones A-E (2-6), and one new adduct composed of an acylphloroglucinol and two β-triketone units, rhotomentosone F (7), as well as five known analogues (8-12). Their structures and absolute configurations were unambiguously determined by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. All isolates were evaluated for their anti-inflammatory and acetylcholinesterase (AChE) inhibitory activities. Compound 6 displayed significant AChE inhibitory effect with an IC50 value of 8.68 μM. Further molecular docking studies of 6 revealed that the interactions with AChE residues Ser125, Glu202, and Tyr133 are crucial for AChE inhibitory activity. The current study not only enriches the chemical diversity of phloroglucinols in Myrtaceae species, but also provides potential lead compounds for the further design and development of new AChE inhibitors to treat Alzheimer's disease.

Keywords: AChE inhibitory effect; Molecular docking; Polymethylated acyphloroglucinols; Rhodomyrtus tomentosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology*
  • Humans
  • Mice
  • Molecular Docking Simulation
  • Molecular Structure
  • Myrtaceae / chemistry*
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / metabolism
  • Phloroglucinol / pharmacology*
  • Plant Leaves / chemistry
  • Protein Binding
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Cholinesterase Inhibitors
  • Phloroglucinol
  • Acetylcholinesterase