title: Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-κB Inhibitory Potential.
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.
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, Bonn D-53115, Germany. henrik-harms@gmx.de.
authors.forename: Henrik
authors.initials: H
authors.lastname: Harms
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea. barbora.orlikova@lbmcc.lu.|Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9 rue Edward Steichen, Luxembourg L-2540, Luxembourg. barbora.orlikova@lbmcc.lu.
authors.forename: Barbora
authors.initials: B
authors.lastname: Orlikova
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea. jsw0525@snu.ac.kr.
authors.forename: Seungwon
authors.initials: S
authors.lastname: Ji
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, Bonn D-53115, Germany. damun1363@hotmail.de.
authors.forename: Damun
authors.initials: D
authors.lastname: Nesaei-Mosaferan
authors.affiliation: Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, Bonn D-53115, Germany. g.koenig@uni-bonn.de.
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: König
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea. marcdiederich@snu.ac.kr.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000818:Animals; D059001:Aquatic Organisms / Q000382:microbiology*; D001203:Ascomycota / Q000378:metabolism*; D001688:Biological Products / Q000494:pharmacology; D047128:Callyspongia / Q000382:microbiology; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects; D005658:Fungi / Q000378:metabolism*; D005912:Gliotoxin / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000494:pharmacology*; D061065:Polyketides / Q000494:pharmacology; D011161:Porifera / Q000382:microbiology
chemical_list: D001688:Biological Products; D016328:NF-kappa B; D010879:Piperazines; D061065:Polyketides; C555444:epipolythiodiketopiperazine; D005912:Gliotoxin; D004247:DNA
keywords: Ascomycete; Dichotomomyces; NF-κB; gliotoxin; leukemia