Microcystilide A: a novel cell-differentiation-promoting depsipeptide from Microcystis aeruginosa NO-15-1840

Microcystis aeruginosa is probably the most deleterious of freshwater bloom-forming cyanobacteria (blue-green algae), posing serious worldwide problems to human and livestock health. A series of hepatotoxic cyclic peptides, the microcystins, has been identified in a number of strains of Microcystis and some other cyanobacteria. All microcystins contain a characteristic beta -amino acid, 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda), or its derivatives, and act as strong protein phosphatase 1 and 2A inhibitors. We have been studying the toxic components of Microcystis aeruginosa NO-15-1840 and have reported microcystin--RR and -LR (cyanoginosin-RR and -LR) as the major toxic components. In this communication, we report the isolation and structural determination of a novel non-Adda-containing cyclic depsipeptide, microcystilide A, from the same organism. Microcystilide A was recognized as a component which causes convulsions or spasms to mice upon intraperitoneal injection. The symptoms were distinctively different from those of the acute toxicity caused by the coexisting microcystins. The compound was found to be only weakly cytotoxic against HCT 116 and HCTVP35 cell lines (IC sub(50) 0.5 mg/mL), but found to be active in the cell-differentiation assay using HL-60 cells at a concentration of 0.5 mg/mL.