TY - JOUR
T1 - Embellicines A and B
T2 - Absolute configuration and NF-κB transcriptional inhibitory activity
AU - Ebrahim, Weaam
AU - Aly, Amal H.
AU - Wray, Victor
AU - Mándi, Attila
AU - Teiten, Marie Hélène
AU - Gaascht, François
AU - Orlikova, Barbora
AU - Kassack, Matthias U.
AU - Lin, Wenhan
AU - Diederich, Marc
AU - Kurtán, Tibor
AU - Debbab, Abdessamad
AU - Proksch, Peter
PY - 2013/4/11
Y1 - 2013/4/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876216959&partnerID=8YFLogxK
U2 - 10.1021/jm400034b
DO - 10.1021/jm400034b
M3 - Article
C2 - 23484593
AN - SCOPUS:84876216959
SN - 0022-2623
VL - 56
SP - 2991
EP - 2999
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 7
ER -