Abstract

The chemical investigation of the secondary metabolites of Paramyrothecium roridum (homotypic synonym: M yrothecium roridum ), an endophytic fungus isolated from the medicinal plant Morinda officinalis , led to the isolation of twelve cytotoxic trichothecene macrolides , including two new ones, named myrothecines H and I. The structures of the new macrolides were elucidated by extensive spectroscopic measurements analyses. In addition, the cytotoxic activities of these compounds were evaluated against SF-268, NCI-H460, and HepG-2 tumor cell lines, and all isolated compounds ( 1−12 ) exhibited significant cytotoxic activity with the IC 50 ranging from 0.0002–16.2 μM. Moreover, the inhibitory activity of myrothecines H and I was evidenced by inducing phosphorylation of JNK (c-Jun N-terminal protein kinase) protein and the PARP (poly ADP-ribose polymerase) cleavage, and eventually induce apoptosis of HepG-2 cells. The results indicated that myrothecines H and I could be applied as chemotherapeutic agents.