| Autor: |
He H; Biosortia Pharmaceuticals , Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States., Bertin MJ; Biosortia Pharmaceuticals , Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States.; Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy , University of Rhode Island , Kingston , Rhode Island 02881 , United States., Wu S; Biosortia Pharmaceuticals , Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States., Wahome PG; Biosortia Pharmaceuticals , Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States., Beauchesne KR; Biosortia Pharmaceuticals , Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States., Youngs RO; Biosortia Pharmaceuticals , Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States., Zimba PV; Center for Coastal Studies , Texas A & M University Corpus Christi , 6300 Ocean Drive , Corpus Christi , Texas 78412 , United States., Moeller PDR; National Oceanic and Atmospheric Administration , Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States., Sauri J; Structure Elucidation, Analytical Research & Development , Merck & Co., Inc. , 126 E. Lincoln Avenue , Rahway , New Jersey 07735 , United States., Carter GT; Biosortia Pharmaceuticals , Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States. |
| Abstrakt: |
Cyanobufalins 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. |
