Potent Algicides Based on the Cyanobacterial Alkaloid Nostocarboline

Abstract

[structure: see text] Nostocarboline and seven derivatives were prepared and displayed minimal inhibitory concentration (MIC) values >or=100 nM against the growth of Microcystis aeruginosa PCC 7806, Synechococcus PCC 6911, and Kirchneriella contorta SAG 11.81, probably via the inhibition of photosynthesis. The natural product hybrid nostocarboline/ciprofloxacin displayed additional antibacterial activity against several Gram-negative bacteria (MICs >or=0.7 microM). Nostocarboline can thus be considered a potent, selective, readily available, natural algicide.

Directed Biosynthesis of Phytotoxic Alkaloids in the Cyanobacterium Nostoc 78–12A

“…Complementing this selective profile, nostocarboline was not determined active against a panel of pathogenic bacteria and fungi. [5] These results substantiated the hypothesis that pathways unique to photoautotrophs and to Plasmodium, potentially through the apicoplast, are targeted by nostocarboline. This potent and selective profile of nostocarboline thus clearly warrants the evaluation of additional derivatives.…”

“…This species is a prototype of a bloom forming cyanobacterium of the genus Microcystis, which is involved in many harmful algal blooms throughout the world. The derivatives 11 and 17-20 were added to growing cultures on day 4 following established assays [5] and the minimal inhibitory concentration was determined as the minimal concentration at which the growth rate of M. aeruginosa is decreased compared to controls. Whereas Br-nostocarboline matched the inhibitory power of nostocarboline (MIC = 1 µM), both the fluorinated and methylated derivatives 17-20 displayed lower activities, with the MIC values increased by one order of magnitude ( Table 1).…”

“…This algicidal activity of Br-nostocarboline 11 was found comparable to the parent nostocarboline (6). [5] After having established that the new derivatives 11 and 17-20 display algicidal effects at concentrations similar or higher than nostocarboline (6), we wanted to investigate the mode of action of nostocarboline (6), and in particular as to whether the observed effects results from inhibition of photosynthesis. In order to test the effects of nostocarboline (6) on photosynthesis, we used chlorophyll-a fluorescence imaging, a non-invasive technique for probing oxygenic photosynthesis.…”

“…[5] Effects of nostocarboline on higher plants were tested in tobacco (Nicotiana tabacum SNN) by infiltration of different concentrations in 6-8 weeks old leaves, exposed to a 14h:10h light/dark cycle, except as noted otherwise. Imaging of photosynthetic parameters from chlorophyll-afluorescence were determined as described previously.…”

“…[3] We have recently isolated the carbolinium alkaloid nostocarboline from the freshwater cyanobacterium Nostoc 78-12A [4] and found strong algicidal effects against competing eukaryotic and prokaryotic photosynthetic organisms. [5] The allelochemical activity of this chlorinated carbolinium [6] is thought to offer competitive advantage to the producing organism through selective inhibition of competitors populating the same habitats. [7] As recognized in recent years, such ecological implications of natural products can open up new avenues for potential therapeutic applications, if corresponding pathways in competitors or grazers and pathogens are targeted.…”