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

Marine Drugs

Henrik Harms¹  Barbora Orlikova²  Seungwon Ji²  Damun Nesaei-Mosaferan¹  Gabriele M. König¹  Marc Diederich² 

[1] Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, Bonn D-53115, Germany; E-Mails:;Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea; E-Mails:

关键词: Ascomycete;    Dichotomomyces;    gliotoxin;    NF-κB;    leukemia;   

DOI  :  10.3390/md13084949

来源: mdpi

【 摘 要 】

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 IC_50s 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.