Neuroprotective trichothecene macrolides from Myrothecium roridum Q6, an endophytic fungus residing in Hypericum perforatum.

Two new macrocyclic trichothecenes named epiroridin acid A (1), and epiroridin acid B (2) together with twelve known compounds (3-14) were isolated from the solid culture of Myrothecium roridum Q6, an endophytic fungus associated with Hypericum perforatum. The structures and absolute configurations of undescribed compounds were elucidated by extensive spectroscopic measurements (UV, MS, and 1D and 2D NMR) analyses, and single-crystal X-ray crystallography. Compounds 1, 4, 6, 8, 13, and 14 were evaluated to be more effective in promoting nerve growth factor (NGF) secretion than the positive drug clenbuterol. Structure-activity relationship analysis showed that the C2-side chain at C-6', and oxidation of double bond at C-2', C-3' in macrocyclic trichothecene could reduce NGF secretory activity, while carboxylation at C-16 is advantageous for enhancing their neuroprotective effects.