title: 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.
authors.affiliation: Marine Biology and Fisheries, Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149, USA. jberry@miami.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Berry
authors.forename: Miroslav
authors.initials: M
authors.lastname: Gantar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gawley
authors.forename: Minglei
authors.initials: M
authors.lastname: Wang
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Rein
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000633:toxicity*; D001156:Artemia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000460:Chlorophyta / Q000187:drug effects; D000458:Cyanobacteria / Q000187:drug effects / Q000378:metabolism*; D005431:Florida; D005618:Fresh Water; D006801:Humans; D008235:Lyngbya Toxins / Q000302:isolation & purification / Q000633:toxicity*; D010456:Peptides, Cyclic; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D015027:Zebrafish
chemical_list: D000900:Anti-Bacterial Agents; D008235:Lyngbya Toxins; D010456:Peptides, Cyclic; C509972:pahayokolide A