title: Embellicines A and B: absolute configuration and NF-κB transcriptional inhibitory activity.
abstract: Two new metabolites, embellicines A and B (1 and 2), were isolated from the EtOAc extract of the fungus Embellisia eureka , an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae). The structures of these new compounds were determined on the basis of extensive one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configuration of embellicine A (1) was determined by TDDFT ECD calculations of solution conformers, whereas that of embellicine B (2) was deduced based on ROESY correlations and on biogenetic considerations in comparison to 1. Both embellicines (1 and 2) are cytostatic, cytotoxic, and inhibit NF-κB transcriptional activity, indicating that inhibition of NF-κB may be a possible mechanism of action of these compounds. Embellicine B (2) was the most active compound encountered in this study and acts at nanomolar concentrations without affecting tumor microenvironment.
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, Geb. 26.23, D-40225 Düsseldorf, Germany.
authors.forename: Weaam
authors.initials: W
authors.lastname: Ebrahim
authors.forename: Amal H
authors.initials: AH
authors.lastname: Aly
authors.forename: Victor
authors.initials: V
authors.lastname: Wray
authors.forename: Attila
authors.initials: A
authors.lastname: Mándi
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Teiten
authors.forename: François
authors.initials: F
authors.lastname: Gaascht
authors.forename: Barbora
authors.initials: B
authors.lastname: Orlikova
authors.forename: Matthias U
authors.initials: MU
authors.lastname: Kassack
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
authors.forename: Tibor
authors.initials: T
authors.lastname: Kurtán
authors.forename: Abdessamad
authors.initials: A
authors.lastname: Debbab
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D007189:Indans / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D007189:Indans; D016328:NF-kappa B; D011760:Pyrrolidinones; C581576:embellicine A; C581577:embellicine B