Urlárins, chlorinated bis-indoles from a benthic mat of cyanobacteria in the West of Ireland.

Cyanobacteria are well-known for producing a diverse array of specialised metabolites, with increasing occurrences due to our changing climate. Though some cyanobacterial proliferations are harmless, others produce toxic compounds with detrimental effects to their surrounding environment including human health. A large cyanobacterial accumulation proliferating at Lough Urlár, Co. Mayo, Ireland, was selected for further chemical analysis owing to the presence of several polychlorinated metabolites detected by LC-MS in the methanolic fraction, which also displayed cytotoxic activity. After deep chemical investigation, a family of previously unreported tetrachlorinated bis-indole alkaloids named urlárins was identified in the extract of this benthic mat. The planar structures were deduced using HRMS and MS/MS analyses, 1D and 2D NMR techniques. As compounds 1-5 display axial chirality arising from restricted rotation around the single bond linking both indole rings, absolute configurations were assigned through comparison of experimental and calculated ECD spectra. During preliminary biological activity assessment, urlárin C (4) displayed acute lethality in an Artemia salina assay with an LC50 of 2.8 ± 0.3 μM. A further pharmacological assessment showed a slight anti-inflammatory activity of several of these compounds, as evidenced by NO inhibition. Additionally, no effect was observed in TRPV1 non-selective cation channels at the studied concentrations, with the exception of urlárin E (7), that produced a slight increase in the currents.