Antillatoxin: An Exceptionally Ichthyotoxic Cyclic Lipopeptide from the Tropical Cyanobacterium Lyngbya majuscula

Journal of the American Chemical Society
1995.0

Abstract

Marine cyanobacteria, particularly those collected from the wild, continue to be exceptionally rich sources of structurally unique and biologically-active natural products. In this regard, we recently reported on our discovery and structural description of curacin A, a potent brine shrimp toxin from a marine cyanobacterium, Lyngbya majuscula, collected in Curagao. Curacin A shows considerable promise as an antiproliferative agent due to its inhibition of tubulin polymerization, a validated mechanism for treatment of neoplastic disorders. However, in addition to brine shrimp toxicity, the crude extract of this L. majuscula collection showed considerable ichthyotoxic (LD50 approximately 25 μg/mL) and molluskicidal (LD50 < 100 μg/mL) activity. Curacin A was not responsible for these other bioactivities; rather, fractionation using the fish and snail bioassays has led to the isolation of two other distinct classes of natural products from this organism. The structure elucidation of the most ichthyotoxic compound, antillatoxin (1, LD50 = 0.05 μg/mL), is the subject of this report, whereas a strongly molluskicidal agent of novel structure, barbaramide A (LD100 = 10 μg/mL), is to be described in a future publication. We speculate that this array of bioactive metabolites functions in nature to protect this cyanobacterium from predation by crustacea, herbivorous fish, and gastropod mollusks which are abundant in the marine habitat in which this organism thrives. Overall, the finding that the various bioactivities associated with the crude extract are due to three distinct classes of structurally novel natural products further attests to the spectacular adaptive and biosynthetic capabilities of cyanobacteria, in general, and this collection of L. majuscula in particular.

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