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

Picrachinentins A-F (-, respectively), six novel cyclopeptide alkaloid-type burpitides (CPABs), were isolated and fully elucidated from the EtOH extract of the stems and leaves of . Structurally, compounds - 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, and ) or hexanoyl (Hexa, , , , and ) 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 HO-damaged SH-SY5Y cells. Compound 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 restored the tyrosine hydroxylase expression in the striatum of the MPTP-damaged mouse brain, which demonstrates its protective effect on dopaminergic neurons.