Inhibitors of BRD4 Protein from a Marine-Derived Fungus Alternaria sp. NH-F6Reportar como inadecuado


Inhibitors of BRD4 Protein from a Marine-Derived Fungus Alternaria sp. NH-F6


Inhibitors of BRD4 Protein from a Marine-Derived Fungus Alternaria sp. NH-F6 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Institute of Marine Biology, Ocean College, Zhejiang University, Zhoushan Campus, No. 1 Zheda Road, Zhoushan 316021, China





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Academic Editor: Orazio Taglialatela-Scafati

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 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. View Full-Text

Keywords: marine-derived fungus; Alternaria sp. NH-F6; secondary metabolites marine-derived fungus; Alternaria sp. NH-F6; secondary metabolites





Autor: Hui Ding, Dashan Zhang, Biao Zhou and Zhongjun Ma *

Fuente: http://mdpi.com/



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