A Collection of Bioactive Nitrogen-Containing Molecules from the Marine Sponge <i>Acanthostrongylophora ingens</i>

Abstract

Thirteen nitrogen-containing molecules (1a/1b and 2−12) were isolated from the Indonesian sponge Acanthostrongylophora ingens, highlighting the richness of this organism as a source of alkaloids. Their structures were elucidated using one- and two-dimensional NMR spectroscopy and HR-ESI-MS, while the stereochemistry of the diketopiperazines was established using Marfey’s method. All compounds were screened in our standard bioactivity assays, including antibacterial, antikinases, and amyloid β-42 assays. The most interesting bioactivity result was obtained with the known acanthocyclamine A (3), which revealed for the first time a specific Escherichia coli antimicrobial activity and an inhibitory effect on amyloid β-42 production induced by aftin-5 and no cytotoxicity at the dose of 26 µM. These results highlight the potentiality of a bipiperidine scaffold as a promising skeleton for preventing or reducing the production of amyloid β-42, a key player in the initiation of Alzheimer’s disease.

Keywords

• <i>Acanthostrongylophora ingens</i>
• marine sponge
• halicyclamine derivative
• diketopiperazine
• alkaloid
• bipiperidine scaffold
• kinase inhibitor
• antimicrobial activity
• inhibitor of amyloid β-42