np8b00736_si_liveslides.zip (8.1 MB)
Cyanobufalins: Cardioactive Toxins from Cyanobacterial Blooms
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posted on 2018-11-08, 21:45 authored by Haiyin He, Matthew J. Bertin, ShiBiao Wu, Paul G. Wahome, Kevin R. Beauchesne, Ross O. Youngs, Paul V. Zimba, Peter D. R. Moeller, Josep Sauri, Guy T. CarterCyanobufalins A–C (1–3), a new series of cardiotoxic steroids, have
been discovered from cyanobacterial blooms in Buckeye Lake and Grand
Lake St. Marys in Ohio. Compounds 1–3 contain distinctive structural features, including geminal methyl
groups at C-4, a 7,8 double bond, and a C-16 chlorine substituent
that distinguish them from plant- or animal-derived congeners. Despite
these structural differences, the compounds are qualitatively identical
to bufalin in their cytotoxic profiles versus cell lines in tissue
culture and cardiac activity, as demonstrated in an impedance-based
cellular assay conducted with IPSC-derived cardiomyocytes. Cyanobufalins
are nonselectively toxic to human cells in the single-digit nanomolar
range and show stimulation of contractility in cardiomyocytes at sub-nanomolar
concentrations. The estimated combined concentration of 1–3 in the environment is in the same nanomolar
range, and consequently more precise quantitative analyses are recommended
along with more detailed cardiotoxicity studies. This is the first
time that cardioactive steroid toxins have been found associated with
microorganisms in an aquatic environment. Several factors point to
a microbial biosynthetic origin for the cyanobufalins.