Epigenetic modifiers induce bioactive phenolic metabolites in the marine-derived fungus Penicillium brevicompactum (original) (raw)
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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 1–9. 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, (IC 50 20 to 30 µg/mL) and antiproliferative activities (IC 50 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.
Marine drugs, 2018
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 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 ⁻. Sodium butyrate also enhanced the productivity of anthranilic acid () and ergosterol peroxide (). The antioxidant as well as the antiproliferative activities of each metabolite were determined. Syringic acid (), sinapic acid (), and acetosyringone () exhibited potent in vitro free radical scavenging, (IC 20 to 30 µg/mL) and antiproliferative activities (IC 1.14 to 1.71 µM) against HepG2 cancer cell line. Furthermore, a...
Chiang Mai Journal of Science
Inhibition of histone deacetylase (HDAC) activity in cancer cells is a promising mechanism for cancer treatment. A screening program for fungi capable of producing HDAC-inhibiting molecules would lead to discovery of potential anticancer agents. The objective of this study was to isolate and characterize fungi capable of producing HDAC inhibitors from soil samples. Only one out of 48 soil fungal isolates exhibited HDAC inhibitory activity. Based on its morphological characteristics and the internal transcribed spacer (ITS) sequence of ribosomal RNA gene, the TS1 fungal isolate was identified as Aspergillus niger and named as A. niger TS1. The cultured medium of strain TS1 significantly inhibited HDAC activity both in vitro and in mammalian cells. The cultured medium of strain TS1 exhibited antiproliferative activity against human acute T cell leukemia cell line (Jurkat cells), human cervical cancer cell line (HeLa cells), and human colon cancer cell line (HCT116 cells). The growth i...
Potential of Anti-Cancer Activity of Secondary Metabolic Products from Marine Fungi
Journal of Fungi, 2021
The promising feature of the fungi from the marine environment as a source for anticancer agents belongs to the fungal ability to produce several compounds and enzymes which contribute effectively against the cancer cells growth. L-asparaginase acts by degrading the asparagine which is the main substance of cancer cells. Moreover, the compounds produced during the secondary metabolic process acts by changing the cell morphology and DNA fragmentation leading to apoptosis of the cancer cells. The current review has analyed the available information on the anticancer activity of the fungi based on the data extracted from the Scopus database. The systematic and bibliometric analysis revealed many of the properties available for the fungi to be the best candidate as a source of anticancer drugs. Doxorubicin, actinomycin, and flavonoids are among the primary chemical drug used for cancer treatment. In comparison, the most anticancer compounds producing fungi are Aspergillus niger, A. fumi...
International Journal of Phytocosmetics and Natural Ingredients
Introduction: As part of cancer research, mycotherapy is a relatively new and promissory source of agents with immunomodulating and antitumor properties. Ongoing research projects are aiming to provide mushrooms as a new generation of "biotherapeutics". In addition to high-molecular weight polysaccharides, efforts should be made to find new anticancer drugs using low-molecular weight secondary metabolites, e.g. phenolic compounds that can inhibit or trigger specific biochemical signals leading to cancer. Methods: An in silico approach based on the structural similarity of low-molecular weight mycocompounds (phenolics) with respect to antitumor substances and molecules with modulatory effects on epigenetic events was used. For the screening of mushroom molecules with potential regulatory effects on epigenome (obtained on Web of Science, August 2015), the enzymes histone acetyltransferase (HAT), histone deacetylase (HDAC) and DNA methyltransferase (DNMT) were chosen as targets. Similarity analysis were performed with the software Saranea. Moreover, the determination of the chemical structural similitude between phenolic compounds of Pleurotus ostreatus (oyster mushroom) and antitumor reference compounds was carried out with the software Power MV 0.61. Tanimoto's coefficients (Tc) similar or higher to 0.90 were considered as significant. Results: Seven mushroom compounds with high structural similarity to reference substances with modulatory activity on epigenetic events (Tc ≥0.90) were identified: 5 with a potential effect on histone acetylation/deacetylation, and 3 acting on the enzyme DNMT. Twenty antitumor reference compounds showed structural similarity to 3 phenols occurring in P. ostreatus, corresponding the largest number to protocatechuic acid and the flavonoids myricetin and naringin. According to its similarity to the antitumor compounds, they would act as DNA antimetabolites, antimitotic, and/or alkylating agents. Conclusion: It seems feasible to harness the natural pool of mushrooms secondary metabolites and to predict by in silico approaches their potential modulatory effects on epigenetic events and antitumor activity, in special phenolics occurring in P. ostreatus. This is an exciting advance for developing nutraceuticals/ cosmeceuticals and innovative drugs.
Natural products from marine fungi for the treatment of cancer
Poster in Vaam Jahrestagung 2011 03 06 04 2011 Karlsruhe Germany, 2011
Marine fungi represent a huge potential for new natural products and an increased number of new metabolites have become known over the past years, while much of the hidden potential still needs to be uncovered. Representative examples of biodiversity studies of marine fungi and of natural products from a diverse selection of marine fungi from the author's lab are highlighting important aspects of this research. If one considers the huge phylogenetic diversity of marine fungi and their almost ubiquitous distribution, and realizes that most of the published work on secondary metabolites of marine fungi has focused on just a few genera, strictly speaking Penicillium, Aspergillus and maybe also Fusarium and Cladosporium, the diversity of marine fungi is not adequately represented in investigations on their secondary metabolites and the less studied species deserve special attention. In addition to results on recently discovered new secondary metabolites of Penicillium species, the diversity of fungi in selected marine habitats is highlighted and examples of groups of secondary metabolites produced by representatives of a variety of different genera and their bioactivities are presented. Special focus is given to the production of groups of derivatives of metabolites by the fungi and to significant differences in biological activities due to small structural changes.
2019
Fungal metabolites with antioxidant and acetylcholinesterase inhibitory activities can be developed as food supplements helpful for treatment of neurodegenerative diseases, like Alzheimer's disease. Fungal biosynthesis depends on the expression of several enzymes that can change chromatin?s conformation, provoking activation or silencing of gene transcription. In this sense, the use of epigenetic modulators, able to alter chromatin?s conformation, has been a modern technique used to induce the expression of silenced genes in fungi. In the present study the metabolic profile and the antioxidant and anti-acetylcholinesterase activities of the extracts of Penicillium flavigenum (PF) and P. tanzanicum (PT) grown in the presence of epigenetic modulators were analyzed. The fungi were grown in liquid media, with or without (control) the epigenetic modulators azacytidine (AZA), hydralazine (HYDRA), procainamide (PRO), suberoyl hydroxamic acid (SAHA) and sodium butyrate (BUT) (500 uM). T...
Metabolites
Cancer is the leading cause of death globally, with an increasing number of cases being annually reported. Nature-derived metabolites have been widely studied for their potential programmed necrosis, cytotoxicity, and anti-proliferation leading to enrichment for the modern medicine, particularly within the last couple of decades. At a more rapid pace, the concept of multi-target agents has evolved from being an innovative approach into a regular drug development procedure for hampering the multi-fashioned pathophysiology and high-resistance nature of cancer cells. With the advent of the Red Sea Penicillium chrysogenum strain S003-isolated indole-based alkaloids, we thoroughly investigated the molecular aspects for three major metabolites: meleagrin (MEL), roquefortine C (ROC), and isoroquefortine C (ISO) against three cancer-associated biological targets Cdc-25A, PTP-1B, and c-Met kinase. The study presented, for the first time, the detailed molecular insights and near-physiological...
Mutation, Chemoprofiling, Dereplication, and Isolation of Natural Products from Penicillium oxalicum
ACS Omega, 2021
Diethyl sulfate (DES)-based chemical mutagenesis was applied on different fungal strains with the aim of diversifying the secondary metabolites. The mutant strain (VRE-MT1) of Penicillium oxalicum was subjected to dereplication (LCMS-based) and isolation of natural products, resulting in obtaining 10 molecules of bioactive potential. Metabolites, viz. tuckolide, methylpenicinoline, 2-acetyl-3,5dihydroxy-4,6-dimethylbenzeneacetic acid, penicillixanthone A, brefeldin A 7-ketone, and antibiotic FD 549, were observed for the first time from P. oxalicum. The results of antimicrobial activity reveal that the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A have potent antibacterial activity against Bacillus subtilis (ATCC 6633) with minimum inhibitory concentration (MIC) values of 16, 64, and 16 μM, respectively, and the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A were found active against Escherichia coli (ATCC 25922), with MIC values of 16, 64, and 16 μM, respectively. Also, the metabolites N-[2-(4-hydroxyphenyl)ethenyl]formamide and tuckolide showed effective antioxidant activity in 2,2-diphenyl-1picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid scavenging assays. The mutant VRE-MT1 was found to have 8.34 times higher quantity of N-[2-(4-hydroxyphenyl)ethenyl]formamide as compared to the mother strain. The DES-based mutagenesis strategy has been found to be a potent tool to diversify the secondary metabolites in fungi.