Autumnalamide, a Prenylated Cyclic Peptide from the Cyanobacterium <i>Phormidium autumnale</i>, Acts on SH-SY5Y Cells at the Mitochondrial Level

Abstract

Filamentous cyanobacteria of the genus <i>Phormidium</i> have been rarely studied for their chemical diversity. For the first time, the cultivable <i>Phormidium autumnale</i> was shown to produce a prenylated cyclic peptide named autumnalamide (<b>1</b>). The structure of this peptide was fully determined after a deep exploration of the spectroscopic data, including NMR and HRMS. Interestingly, a prenyl moiety was located on the guanidine end of the arginine amino acid. The absolute configurations of most amino acids were assessed using enantioselective GC/MS analysis, with ¹³C NMR modeling being used for the determination of d-arginine and d-proline. The effects of <b>1</b> on sodium and calcium fluxes were studied in SH-SY5Y and hNav 1.6 HEK cells. When the Ca²⁺ influx was stimulated by thapsigargin, strong inhibition was observed in the presence of <b>1</b>. As a consequence, this compound may act by disrupting the normal calcium uptake of this organelle, inducing the opening of the mitochondrial permeability transition pore, which results in the indirect blockade of store-operated channels