Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades

Abstract

The genus of filamentous cyanobacteria, Lyngbya, has been found to be a rich source of bioactive metabolites. However, identification of such compounds from Lyngbya has largely focused on a few marine representatives. Here, we report on the pharmacology and toxicology of pahayokolide A from a freshwater isolate, Lyngbya sp. strain 15-2, from the Florida Everglades. Specifically, we investigated inhibition of microbial representatives and mammalian cell lines, as well as toxicity of the compound to both invertebrate and vertebrate models. Pahayokolide A inhibited representatives of Bacillus, as well as the yeast, Saccharomyces cerevisiae. Interestingly, the compound also inhibited several representatives of green algae that were also isolated from the Everglades. Pahayokolide A was shown to inhibit a number of cancer cell lines over a range of concentrations (IC50 varied from 2.13 to 44.57 microM) depending on the cell-type. When tested against brine shrimp, pahayokolide was only marginally toxic at the highest concentrations tested (1 mg/mL). The compound was, however, acutely toxic to zebrafish embryos (LC50=2.15 microM). Possible biomedical and environmental health aspects of the pahayokolides remain to be investigated; however, the identification of bioactive metabolites such as these demonstrates the potential of the Florida Everglades as source of new toxins and drugs.

Fig. 1

Inhibition of the green alga Chlamydomonas Ev-29 by pahayokolide A. Chlamydomonas Ev-29 grown in BG-11 medium with pahayokolide A at 1, 5, 10, 15, 20, 25 and 30 μg/mL or MeOH only (bControlQ) in 96-well plates. Growth of the alga was measured daily for 3 days by absorbance (420 nm) using a plate reader.

Fig. 2

Mortality of zebrafish (D. rerio) embryos at 1 and 5 days postfertilization (dpf; A and B, respectively) exposed to pahayokolide A (1, 2, 3, 5 and 10 μg/mL or control (0.1% MeOH only). Embryos (4- to 32-cell stage) exposed at 0 dpf in four replicates per treatment of five embryos per replicate in 1 mL of ERS (see Materials and methods). Squares represent mean percent mortality ± S.E.M. for each group of replicates.