Fluorescence Activity-Guided Isolation of Aaptamine Derivatives From the Marine Sponge <i>Aaptos suberitoides</i> and Their Inhibitory Activity Against Transient Receptor Potential Ankyrin 1

Abstract

Objective: The aim of this research was to isolate and identify the natural products responsible for the biological and fluorescence activity of the extract from the marine sponge Aaptos suberitoides. Methods: Fluorescence activity-guided separation was performed after validation of the inhibitory activity of the extract against human transient receptor potential ankyrin 1 (hTRPA1) and subsequent measurement of its fluorescence activity. Three previously reported marine alkaloids, aaptamine, isoaaptamine, and 9-O-demethylaaptamine, were obtained and identified based on their nuclear magnetic resonance and high-resolution mass spectrometry data. Results: Aaptamine showed emission of the fluorescent light at a wavelength of 485 nm with a quantum yield of 31%. Isoaaptamine and 9-O-demethylaaptamine showed marginal fluorescence activity but promising inhibitory activity against hTRPA1 with IC50 values of 3.1 and 3.9 μM, respectively. Conclusions: This research demonstrates that natural fluorophores can be discovered in living organisms through photoactivity-guided isolation. Aaptamine, isolated as a result, provides an additional 1,6-naphthyridine fluorophore, while isoaaptamine and 9-O-demethylaaptamine suggest a chemical scaffold that could be used to study the function of ion channels.