2. Academic Validation
  3. Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-κB Inhibitory Potential

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

  • Mar Drugs. 2015 Aug 6;13(8):4949-66. doi: 10.3390/md13084949.
Henrik Harms 1,  Barbora Orlikova 2 3,  Seungwon Ji 4,  Damun Nesaei-Mosaferan 5,  Gabriele M König 6,  Marc Diederich 7
Affiliations

Affiliations

  • 1 Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, Bonn D-53115, Germany. henrik-harms@gmx.de.
  • 2 Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea. barbora.orlikova@lbmcc.lu.
  • 3 Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9 rue Edward Steichen, Luxembourg L-2540, Luxembourg. barbora.orlikova@lbmcc.lu.
  • 4 Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea. jsw0525@snu.ac.kr.
  • 5 Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, Bonn D-53115, Germany. damun1363@hotmail.de.
  • 6 Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, Bonn D-53115, Germany. g.koenig@uni-bonn.de.
  • 7 Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea. marcdiederich@snu.ac.kr.
PMID: 26258781 DOI: 10.3390/md13084949
Abstract

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.

Keywords

Ascomycete; Dichotomomyces; NF-κB; gliotoxin; leukemia.

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