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Mar. Drugs 2018, 16(8), 253; https://doi.org/10.3390/md16080253

Epigenetic Modifiers Induce Bioactive Phenolic Metabolites in the Marine-Derived Fungus Penicillium brevicompactum

1
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11787, Egypt
2
Pharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt
3
Pharmacognosy Department, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt
4
Marine Biodiscovery Centre, University of Aberdeen, Aberdeen, Scotland AB24 3UE, UK
5
School of Computing, Engineering and Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK
6
Marine Invertebrates, National Institute of Oceanography and Fisheries, Red Sea Branch, Hurghada 84511, Egypt
7
Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
*
Author to whom correspondence should be addressed.
Received: 20 June 2018 / Revised: 19 July 2018 / Accepted: 28 July 2018 / Published: 30 July 2018
(This article belongs to the Special Issue Strategies for Enhancing the Metabolome of Marine-Derived Fungi)
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Abstract

Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture conditions. These cryptic genes could be expressed for a wide variety of bioactive compounds. One of the recent approaches to induce production of such cryptic fungal metabolites is to use histone deacetylases (HDACs) inhibitors. In the present study, the cultures of the marine-derived fungus Penicillium brevicompactum treated with nicotinamide and sodium butyrate were found to produce a lot of phenolic compounds. Nicotinamide treatment resulted in the isolation and identification of nine compounds 19. Sodium butyrate also enhanced the productivity of anthranilic acid (10) and ergosterol peroxide (11). The antioxidant as well as the antiproliferative activities of each metabolite were determined. Syringic acid (4), sinapic acid (5), and acetosyringone (6) exhibited potent in vitro free radical scavenging, (IC50 20 to 30 µg/mL) and antiproliferative activities (IC50 1.14 to 1.71 µM) against HepG2 cancer cell line. Furthermore, a pharmacophore model of the active compounds was generated to build up a structure-activity relationship. View Full-Text
Keywords: HDACs inhibitors; Penicillium brevicompactum; phenolic metabolites; nicotinamide; sodium butyrate; antiproliferative; pharmacophore HDACs inhibitors; Penicillium brevicompactum; phenolic metabolites; nicotinamide; sodium butyrate; antiproliferative; pharmacophore
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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El-Hawary, S.S.; Sayed, A.M.; Mohammed, R.; Hassan, H.M.; Zaki, M.A.; Rateb, M.E.; Mohammed, T.A.; Amin, E.; Abdelmohsen, U.R. Epigenetic Modifiers Induce Bioactive Phenolic Metabolites in the Marine-Derived Fungus Penicillium brevicompactum. Mar. Drugs 2018, 16, 253.

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