New depsipeptides and brominated macrolides from cultured marine cyanobacteria

Abstract

Laboratory culture of two cyanobacteria isolated from the Panamanian mixed cyanobacterial assemblage that yielded the potent cancer cell toxin coibamide A has lead to the characterization of seven new glycosidic macrolides and seven depsipeptides. The production of these metabolites varies under different culture conditions, and when the cyanobacteria are co-cultured versus grown separately. Comprehensive NMR spectroscopy and HR-TOF-MS established that the glycosidic macrolides are related to the known cytotoxins lyngbouilloside and lyngbyalosides A-C, and are thus named lyngbyalosides D-J. The biosynthetic source of these macrolides is proposed to be the minor cyanobacterial partner, phylogenetic analysis of which suggests that it is a Phormidium species. The relative configuration of lyngbyalosides D-J was determined using J-based analysis and ROESY correlations, as well as comparison with the literature. Five new depsipeptides have also been identified from culture and closely resemble two unreported depsipeptides, named symtropamides A and B, that were previously isolated from the field-collected cyanobacterial assemblage. Symtropamides A and B display preliminary antimalarial activity, which will be investigated further using all seven analogs. The biosynthetic source of these depsipeptides is likely the coibamide-producing cyanobacterium, which is related to the genus Symploca, but may warrant assignment to a separate new genus.