Chemical epigenetic modification uncovers new isocoumarins from the endophyte Dothideomycetes sp. BMC-101

Four new isocoumarin derivatives including two pair of enantiomers [(±)- dothideomarins A (1a/1b) and B (2a/2b)], as well as two related analogs, dothideomarins C and D (3 and 4), were isolated from the endophytic fungus Dothideomycetes sp. BMC-101 obtained from Magnolia grandiflora L. by applying the OSMAC (One Strain Many Compounds) strategy combined with MS/MS-based molecular networking. The enantiomeric pairs existed as racemic or partially racemic mixtures and were obtained by chiral HPLC separation. Their structures were elucidated by comprehensive spectroscopic data analysis, single-crystal X-ray diffraction, and comparison of the experimental and computed ECD curves. Biological screening of all the compounds found that compounds 1a and 2a exhibited moderate to weak cytotoxic activity against U87, A549, SW1990 and HCT-116 cells lines, with IC₅₀ values ranging from 31.9 to 48.1 µM.