title: Inhibitors of BRD4 Protein from a Marine-Derived Fungus Alternaria sp. NH-F6.
abstract: 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 ofAlternariasp. 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 compound2exhibited 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.
authors.affiliation: Institute of Marine Biology, Ocean College, Zhejiang University, Zhoushan Campus, No. 1 Zheda Road, Zhoushan 316021, China. snnu_dh@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Institute of Marine Biology, Ocean College, Zhejiang University, Zhoushan Campus, No. 1 Zheda Road, Zhoushan 316021, China. 21634129@zju.edu.cn.
authors.forename: Dashan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Marine Biology, Ocean College, Zhejiang University, Zhoushan Campus, No. 1 Zheda Road, Zhoushan 316021, China. zhoubiaotd@sina.com.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Institute of Marine Biology, Ocean College, Zhejiang University, Zhoushan Campus, No. 1 Zheda Road, Zhoushan 316021, China. mazj@zju.edu.cn.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000528:Alternaria / Q000737:chemistry*; D059001:Aquatic Organisms / Q000737:chemistry*; D001685:Biological Factors / Q000737:chemistry* / Q000494:pharmacology*; D005658:Fungi / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014157:Transcription Factors / Q000037:antagonists & inhibitors*
chemical_list: D001685:Biological Factors; D014157:Transcription Factors
keywords: Alternaria sp. NH-F6; marine-derived fungus; secondary metabolites