Types A and D Trichothecene Mycotoxins from the Fungus Myrothecium roridum

Abstract

Chromatographic separation of extracts from the fungal biomass of a plant pathogenic fungus, Myrothecium roridum, yielded 8 trichothecene toxins including 6 type D trichothecenes (1 - 6) and 2 type A trichothecenes (7 - 8). 6′,12′-Epoxymyrotoxin A (1) and 7′-hydroxymytoxin B (2) were new macrocyclic trichothecenes, while the other trichothecenes were identified as myrotoxin B (3), myrotoxin D hydrate (4), 2′,3′-epoxymyrothecine A (5), miotoxin A (6), and 2 trichothecenes lacking the macrocyclic lactone system, roridin L-2 (7) and trichoverritone (8). The structures of these mycotoxins were characterized using spectroscopic methods. The absolute configurations of 1 and 2 were determined by NOESY and a comparison of their experimental and calculated ECD spectra. Most of these mycotoxins (1 - 4 and 6) exhibited highly potent antimalarial activity against Plasmodium falciparum. They also showed strong cytotoxicity towards KB and NCI-H187 cell lines (IC 50 0.60-112.28 nM), as well as the Vero cell line (IC 50 1.50-46.51 nM).