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.