Herbarin

Prospective Leads from Endophytic Fungi for Anti-Inflammatory Drug Discovery.[Pubmed:32334437]

Planta Med. 2020 Apr 25.

A wide array of therapeutic effects has been exhibited by compounds isolated from natural sources. "Bio-actives of endophytic origin" is a recently explored area that came into recognition over the last 2 decades. Literature search on the secondary metabolites of endophytes have shown several pharmacologically active compounds especially anti-inflammatory compounds, which have been reviewed in the present paper. The article is structured based on the chemical classification of secondary metabolites. The compounds were identified to possess activity against a total of 16 anti-inflammatory targets. The most common targets involved were NO, TNF-alpha, and inhibition of total ROS. Further, the article gives a detailed insight into the compounds, their endophytic source, and anti-inflammatory target as well as potency. The contents of the article cover all the scientific reports published until Feb. 2019. Thus 118 compounds and 6 extracts have been reported to be obtained from endophytic sources showing anti-inflammatory activities. Amongst these, Herbarin, periconianone A, and periconianone B were identified as the most potent compounds in terms of their IC50 values against NO inhibition.

Modulation of polyketide biosynthetic pathway of the endophytic fungus, Anteaglonium sp. FL0768, by copper (II) and anacardic acid.[Pubmed:31354886]

Phytochem Lett. 2018 Dec;28:157-163.

In an attempt to explore the biosynthetic potential of endosymbiotic fungi, the secondary metabolite profiles of the endophytic fungus, Anteaglonium sp. FL0768, cultured under a variety of conditions were investigated. In potato dextrose broth (PDB) medium, Anteaglonium sp. FL0768 produced the heptaketides, herbaridine A (1), Herbarin (2), 1-hydroxydehydroHerbarin (3), scorpinone (4), and the methylated hexaketide 9S,11R-(+)-ascosalitoxin (5). Incorporation of commonly used epigenetic modifiers, 5-azacytidine and suberoylanilide hydroxamic acid, into the PDB culture medium of this fungus had no effect on its secondary metabolite profile. However, the histone acetyl transferase inhibitor, anacardic acid, slightly affected the metabolite profile affording scorpinone (4) as the major metabolite together with 1-hydroxydehydroHerbarin (3) and a different methylated hexaketide, ascochitine (6). Intriguingly, incorporaion of Cu(2+) into the PDB medium enhanced production of metabolites and drastically affected the biosynthetic pathway resulting in the production of pentaketide dimers, palmarumycin CE4 (7), palmarumycin CP4 (8), and palmarumycin CP1 (9), in addition to ascochitine (6). The structure of the new metabolite 7 was established with the help of spectroscopic data and by MnO2 oxidation to the known pentaketide dimer, palmarumycin CP3 (10). Biosynthetic pathways to some metabolites in Anteaglonium sp. FL0768 are presented and possible effects of AA and Cu(2+) on these pathways are discussed.

Total synthesis of Herbarin A and B, determination of their antioxidant properties and toxicity in zebrafish embryo model.[Pubmed:25690788]

Bioorg Med Chem Lett. 2015 Mar 15;25(6):1192-5.

Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model.

The synthesis of the pyranonaphthoquinones dehydroherbarin and anhydrofusarubin using Wacker oxidation methodology as a key step and other unexpected oxidation reactions with ceric ammonium nitrate and salcomine.[Pubmed:22915091]

Org Biomol Chem. 2012 Oct 14;10(38):7809-19.

The synthesis of two closely related pyranonaphthoquinones, dehydroHerbarin and anhydrofusarubin, is described. The construction of the naphthalene nuclei was achieved using the Stobbe condensation reaction using 2,4-dimethoxybenzaldehyde and 2,4,5-trimethoxybenzaldehyde as their respective starting materials. Two key steps en route include a PIFA-mediated addition of a methoxy substituent onto the naphthalene skeleton and a Wacker oxidation reaction to construct the benzo[g]isochromene nucleus. Two interesting oxidation reactions of the intermediate isochromene enol ether of 7,9-dimethoxy-3-methyl-1H-benzo[g]isochromene-5-ol were observed. Treatment of the substrate with salcomine resulted in the formation of (3-formyl-4-hydroxy-6,8-dimethoxynaphthalene-2-yl)methyl acetate, while treatment of the same substrate with CAN resulted in the formation of racemic (3R,4R)-3-hydroxy-7,9-dimethoxy-3-methyl-5,10-dioxo-3,4,5,10-tetrahydro-1H-benzo[ g]isochromen-4-yl nitrate.

Maximizing chemical diversity of fungal metabolites: biogenetically related Heptaketides of the endolichenic fungus Corynespora sp. (1).[Pubmed:20521776]

J Nat Prod. 2010 Jun 25;73(6):1156-9.

In an attempt to explore the biosynthetic potential of the endolichenic fungus Corynespora sp. BA-10763, its metabolite profiles under several culture conditions were investigated. When cultured in potato dextrose agar, it produced three new heptaketides, 9-O-methylscytalol A (1), 7-desmethylHerbarin (2), and 8-hydroxyHerbarin (3), together with biogenetically related metabolites scytalol A (4), 8-O-methylfusarubin (5), scorpinone (6), and 8-O-methylbostrycoidin (7), which are new to this organism, and Herbarin (8), a metabolite previously encountered in this fungal strain. The use of malt extract agar as the culture medium led to the isolation of 6, 8, 1-hydroxydehydroHerbarin (9), and 1-methoxydehydroHerbarin (10), which was found to be an artifact formed during the extraction of the culture medium with methanol. The structures of all new compounds were determined by interpretation of their spectroscopic data and chemical interconversions.

New naphthoquinone derivatives from the ascomycete IBWF79B-90A.[Pubmed:19323262]

Z Naturforsch C J Biosci. 2009 Jan-Feb;64(1-2):25-31.

Bioactivity-guided fractionation of extracts from the fungus IBWF79B-90A resulted in the isolation of three known naphthoquinones, Herbarin, dehydroHerbarin, and O-methylHerbarin and the azaanthraquinone scorpinone as well as three structurally related derivatives, O-phenethylHerbarin and herbaridines A and B. All seven compounds exhibited cytotoxic activities against several cell lines.

Biosynthesis of scorpinone, a 2-azaanthraquinone from Amorosia littoralis, a fungus from marine sediment.[Pubmed:18281953]

J Nat Prod. 2008 Mar;71(3):426-30.

The biogenetic origin of the carbon atoms in the 2-azaanthraquinone scorpinone ( 1), produced by the rare fungus Amorosia littoralis isolated from marine sediment, was explored through isotopic enrichment studies utilizing [2- (13)C]-acetate and [1,2- (13)C]-acetate. The labeling results reveal a heptaketide precursor is involved in the biosynthesis of 1, as has been found for the structurally related naphthoquinone dihydrofusarubin. The previously identified naphthoquinone Herbarin ( 2) was also isolated and appears to bear the same biogenetic relationship to 1 as the fusarubins do to the fungal 2-azaanthraquinone bostrycoidins.

Heptaketides from Corynespora sp. inhabiting the cavern beard lichen, Usnea cavernosa: first report of metabolites of an endolichenic fungus.[Pubmed:17988097]

J Nat Prod. 2007 Nov;70(11):1700-5.

Two new heptaketides, corynesporol (1) and 1-hydroxydehydroHerbarin (2), along with Herbarin (3) were isolated from an endolichenic fungal strain, Corynespora sp. BA-10763, occurring in the cavern beard lichen Usnea cavernosa. The structures of 1-3 were elucidated from their spectroscopic data. Aerial oxidation of corynesporol (1) yielded Herbarin (3). Acetylation of 1 afforded the naphthalene derivative 4, whereas acetylation of 3 gave the corresponding naphthoquinone 6 and dehydroHerbarin (5). All compounds were evaluated for their cytotoxicity and ability to inhibit migration of human metastatic breast and prostate cancer cell lines MDA-MB-231 and PC-3M, respectively. DehydroHerbarin (5) inhibited migration of both cell lines at concentrations not toxic to these cell lines. This is the first report of metabolites from an endolichenic fungus.

New metabolites from sponge-derived fungi Curvularia lunata and Cladosporium herbarum.[Pubmed:12027752]

J Nat Prod. 2002 May;65(5):730-3.

The fungus Curvularia lunata, isolated from the marine sponge Niphates olemda, yielded the new 1,3,8-trihydroxy-6-methoxyanthraquinone, which we named lunatin (1), the known modified bisanthraquinone cytoskyrin A (2), and the known plant hormone (+)-abscisic acid (3). Both anthraquinones were found to be active against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Two strains of the fungus Cladosporium herbarum, isolated from the sponges Aplysina aerophoba and Callyspongia aerizusa, respectively, yielded two new alpha-pyrones, Herbarin A (4) and Herbarin B (5), the known compound citreoviridin A (6), and the new phthalide herbaric acid (7). All structures were unambiguously established by 1D and 2D NMR and MS data.

Synthesis of two naphthoquinone antibiotics, dehydroherbarin and 6-deoxybostrycoidin.[Pubmed:10813991]

J Org Chem. 2000 Feb 11;65(3):640-4.

The synthesis of two naphthoquinone antibiotics, dehydroHerbarin (7) and 6-deoxybostrycoidin (5), was accomplished by reaction of 3-acetonyl-2-bromomethyl-6,8-dimethoxy-1,4-naphthoquinone (23) with either triethylamine or ammonia, respectively. This is the first report on their synthesis.