10.1021/acs.jnatprod.8b00736.ls01
Haiyin He
Haiyin
He
Matthew J. Bertin
Matthew J.
Bertin
ShiBiao Wu
ShiBiao
Wu
Paul G. Wahome
Paul
G. Wahome
Kevin R. Beauchesne
Kevin R.
Beauchesne
Ross O. Youngs
Ross O.
Youngs
Paul V. Zimba
Paul V.
Zimba
Peter D. R. Moeller
Peter
D. R. Moeller
Josep Sauri
Josep
Sauri
Guy T. Carter
Guy T.
Carter
Cyanobufalins: Cardioactive Toxins from Cyanobacterial
Blooms
American Chemical Society
2018
cardiomyocyte
C -16 chlorine substituent
nanomolar range
Several factors point
geminal methyl groups
concentration
Grand Lake St
Cyanobacterial Blooms Cyanobufalins
2018-11-08 21:45:18
Media
https://acs.figshare.com/articles/media/Cyanobufalins_Cardioactive_Toxins_from_Cyanobacterial_Blooms/7318676
Cyanobufalins A–C (<b>1</b>–<b>3</b>), a new series of cardiotoxic steroids, have
been discovered from cyanobacterial blooms in Buckeye Lake and Grand
Lake St. Marys in Ohio. Compounds <b>1</b>–<b>3</b> 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 <b>1</b>–<b>3</b> 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.