Discovery of novel natural cardiomyocyte protectants from a toxigenic fungus Stachybotrys chartarum

Stachybatranones A - F ( 1a / 1b and 2 - 6 ) and three known analogues, namely methylatranones A and B ( 7 and 8 ) and atranone B ( 9 ), were isolated and identified from a toxigenic fungus Stachybotrys chartarum . Their structures and absolute configurations were elucidated via the extensive spectroscopic data, comparison of the experimental electronic circular dichroism (ECD) data, and single -crystal X-ray diffraction analyses. Structurally, compounds 2 - 6 belonged to a rare class of C-alkylated dolabellanes, featuring a unique five -membered hemiketal ring and a gamma-butyrolactone moiety both fused to an 11 -membered carbocyclic system, while compound 1 ( 1a / 1b ) represented the first example of a 5 -11 -6 -fused atranone possessing a 2,3-butanediol moiety. The cardiomyocyte protective activity assay revealed that compounds 1 - 9 ameliorated cold ischemic injury at 24 h post cold ischemia (CI), with compounds 1 and 4 acting in a dose -dependent manner. Moreover, compound 1 prevented cold ischemia induced dephosphorylation of PI3K and AKT acting in a dose -dependent manner. In this study, a new class of natural products were found to protect cardiomyocytes against cold ischemic injury, providing a potential option for the development of novel cardioprotectants in heart transplant medicine.