Cytotoxic and non-cytotoxic exometabolites of the cyanobacterium Nostoc insulare

The isolation, identification and quantification of exometabolites from culture media of the cyanobacterium Nostoc insulare are described. Besides the known exometabolite 4,4'-dihydroxybiphenyl (I), two more compounds, the beta-carboline 9H-pyrido(3,4-b) indole (norharmane, II) and N,N'-(4,5-dimethyl-1,2-phenylene) bis-acetamide (III), were discovered. Concentrations of all three compounds in media and biomass of five 250 L cultures of N. insulare were determined. Culture medium values for I ranged between 200 and 1,250 mu g L-1 (1.1-6.7 mu mol L-1), for III between 115 and 390 mu g L-1 (0.5-1.8 mu mol L-1), whereas concentrations of II were conspicuously lower (2-16 mu g L-1 or 0.014-0.094 mu mol L-1). Amounts of III per volume of culture medium were about tenfold higher than in the biomass contained in an equal culture volume. This difference is an indication for an active excretion of III. Amounts of I and II in biomass and media were of no significant difference. In the neutral red uptake assay, I and II were found to be toxic against eukaryotic cells as follows: I was of considerable cytotoxicity in concentrations from 1,000 to 10 mg L-1 and of lower cytotoxicity (causing a 27% decrease of cell viability) in a concentration of 1,000 mu g L-1, whereas II was merely of considerable cytotoxicity in concentrations from 1,000 to 100 mg L-1. Because of the cytotoxicity of I and because of the many known pharmacological effects of II there is a possibility that a certain amount of risk to humans and livestock comes from cultures or even from biomass-free culture media of N. insulare. The natural function of the examined exometabolites is discussed.