Sponge fluorescent molecules and synthetic derivatives used for live imaging of neurons, tissues and organisms. What is their natural role?
Marine sponges are known to produce different bioactive secondary metabolites. One substance out of this group is a brominated pyrrole imidazole alkaloid, which showed anti-angiogenic activity and was later described to be a pH sensitive live imaging dye. This compound, Ageladine A, permeates membranes when uncharged and the two fold bromination seems to be a very important factor increasing its membrane permeability. In acidic cellular compartments or organs Ageladine A is protonated and is trapped and not expelled by MDR and MRP transporters, which are present in eukaryotic cells. Given the interesting properties of Ageladine A we synthetized twenty-five derivatives of which several are brightly fluorescent. Some compounds are as well pH sensitive and at least one allows ratiometric measurements over a wide pH range. As metabolic states like hypoxia or apoptosis are reflected by the cytosolic pH values, these dyes can be used to indicate the viability of cells. The major increase of fluorescence of Ageladine A and its sensitivity is in the pH range of pH 5 to pH 7, which is most interesting range for physiological measurements. Due to the non-toxic properties the dyes can be used to stain whole animals (transparent aquatic animals), tissues and e.g. astrocytes and cultured neuronal cells. The very high quantum yield of the natural product Ageladine A and some derivatives raises the question to its function in sponges. We propose fluorescing compounds in sponge cells to act in symbioses with autotroph organism to convert UV/blue light to longer wavelength in high efficiency, which supplies autotroph organisms to highly effective blue/green light for photosynthesis.