Amphiphilic Polyamine α-Synuclein Aggregation Inhibitors from the Sponge Aaptos lobata

Abstract

Bioassay-guided investigation of the sponge Aaptos lobata resulted in the isolation and identification of two new amphiphilic polyamines, aaptolobamines A (1) and B (2). Their structures were determined through analysis of NMR and MS data. MS analysis also indicated that A. lobata contained a complex mixture of aaptolobamine homologues. Both aaptolobamines A (1) and B (2) show broad bioactivity, including cytotoxicity against cancer cell lines, moderate antimicrobial activity against a methicillin-resistant strain of Staphylococcus aureus, and weak activity against a Pseudomonas aeruginosa strain. The mixtures of aaptolobamine homologues were shown to contain compounds that bind to the Parkinson's disease associated amyloid protein α-synuclein and inhibit its aggregation.

α-Synuclein Aggregation Inhibitory and Antiplasmodial Activity of Constituents from the Australian Tree Eucalyptus cloeziana

“…By contrast, the more widely recognized through-space ROE correlations used to establish relative configurations occur as in-phase correlations. We have previously used ROESY data to identify interconverting cis/trans amides and molecules containing strong intramolecular hydrogen-bonding networks that generate conformationally restricted rotamers. − Using this technique, 1 was confirmed as a single interconverting molecule with resonances associated with four rotamers. Careful analysis of the 1D and 2D NMR data for myrtucommulone P ( 1 ) enabled the structure assignment of four rotamers ( 1a – d ) and their relative configurations (Figure ).…”