Bromodomains (BRD) are readers of the epigenetic code that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Recently, bromodomain-containing proteins such as BRD4 have been demonstrated to be druggable through the discovery of potent inhibitors. These protein-protein interaction inhibitors have the potential to modulate multiple diseases by their profound anti-inflammatory and antiproliferative effects. In order to explore new BRD4 inhibitors as well as lead compounds for the development of new drugs, the secondary metabolites of Alternaria sp. NH-F6, a fungus isolated from deep-sea sediment samples, were analyzed systematically. Five new compounds including two new perylenequinones (1-2), one new alternaric acid (3), 2-(N-vinylacetamide)-4-hydroxymethyl-3-ene-butyrolactone (4), one new cerebroside (5), together with 19 known compounds (6-24) were isolated from the ethyl acetate extracts of this strain. Their structures were elucidated using nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectrometry (HR-ESI-MS) analyses. Finally, all these compounds were evaluated for their inhibitory activity against BRD4 protein, and compound 2 exhibited a potent inhibition rate of 88.1% at a concentration of 10 µM. This research provides a new BRD4 inhibitor which may possess potential antitumoral, antiviral, or anti-inflammatory pharmaceutical values.
secondary metabolites, marine-derived fungus, Alternaria sp. NH-F6
NCBI PubMed ID: 28300771Publication DOI: 10.3390/md15030076Journal NLM ID: 101213729Publisher: Basel, Switzerland: Molecular Diversity Preservation International
Correspondence: Ding H
; Zhang D <21634129@zju.edu.cn>, Zhou B ; Ma Z
Institutions: Institute of Marine Biology, Ocean College, Zhejiang University, Zhoushan, China
Methods: 13C NMR, 1H NMR, HPLC, UV, HR-ESI-MS, HMBC, COSY, HSQC
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