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 (IC₅₀ 0.60 - 112.28 nM), as well as the Vero cell line (IC₅₀ 1.50 - 46.51 nM).