Picrachinentins A-F, 14-Membered Cyclopeptide Alkaloid-Type Burpitides with Uncommon N-Terminal Modifications from Picrasma chinensis and Their Neuroprotective Activity

Org Lett. 2024 Jun 7;26(22):4672-4677. doi: 10.1021/acs.orglett.4c01390. Epub 2024 May 24.

Abstract

Picrachinentins A-F (1-6, respectively), six novel cyclopeptide alkaloid-type burpitides (CPABs), were isolated and fully elucidated from the EtOH extract of the stems and leaves of Picrasma chinensis. Structurally, compounds 1-6 have a 14-membered paracyclophane ring system that was closed through an ether bond between the β-hydroxy amino acid and tyrosine and modified with a 4,5-methylenedioxybenzoyloxy (MDBz, 3 and 5) or hexanoyl (Hexa, 1, 2, 4, and 6) group at the N-terminus. Interestingly, this is the first report on the isolation and characterization of CPABs from plants of the Simaroubaceae family. In addition, all compounds showed a neuroprotective effect against H2O2-damaged SH-SY5Y cells. Compound 1 was further investigated for its neuroprotective activities using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease animal model, and it dramatically improved MPTP-impaired motor behavioral performance. Biochemical analysis revealed compound 1 restored the tyrosine hydroxylase expression in the striatum of the MPTP-damaged mouse brain, which demonstrates its protective effect on dopaminergic neurons.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Alkaloids* / chemistry
  • Alkaloids* / isolation & purification
  • Alkaloids* / pharmacology
  • Animals
  • Humans
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / pharmacology
  • Mice
  • Molecular Structure
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / isolation & purification
  • Neuroprotective Agents* / pharmacology
  • Peptides, Cyclic* / chemistry
  • Peptides, Cyclic* / isolation & purification
  • Peptides, Cyclic* / pharmacology
  • Picrasma* / chemistry
  • Plant Leaves / chemistry

Substances

  • Neuroprotective Agents
  • Peptides, Cyclic
  • Alkaloids
  • Hydrogen Peroxide
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine