Aß-42 lowering agents from the marine-derived fungus Dichotomomyces cejpii.

The ascomycete Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. Three new steroids (1-3), two of which are present as glycosides, with an untypical pattern of carbon-carbon double bounds, were obtained from fungal extracts, as well as the known xanthocillin X dimethyl ether (4). Compounds 2 and 4 were evaluated in an Alzheimer's disease cellular assay and found capable of preventing the enhanced production of amyloid ß-42 in Aftin-5 treated cells. Aß-42 lowering agents are considered as candidates for the treatment of neurodegenerative Alzheimer's disease.

Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-κB Inhibitory Potential.

The Ascomycota Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. A new gliotoxin derivative, 6-acetylmonodethiogliotoxin (1) was obtained from fungal extracts. Compounds 2 and 3, methylthio-gliotoxin derivatives were formerly only known as semi-synthetic compounds and are here described as natural products. Additionally the polyketide heveadride (4) was isolated. Compounds 1, 2 and 4 dose-dependently down-regulated TNFα-induced NF-κB activity in human chronic myeloid leukemia cells with IC50s of 38.5 ± 1.2 µM, 65.7 ± 2.0 µM and 82.7 ± 11.3 µM, respectively. The molecular mechanism was studied with the most potent compound 1 and results indicate downstream inhibitory effects targeting binding of NF-κB to DNA. Compound 1 thus demonstrates potential of epimonothiodiketopiperazine-derived compounds for the development of NF-κB inhibitors.