•One strain-many compounds (OSMAC) strategy was applied by adding CuCl2 to fermentation medium.•Two new citrinin derivatives were isolated from the fermentation extracts of Penicillium Citrinum Salicorn 46.•One of citrinin derivatives exhibits potent cytotoxic activities against A549 and HepG2 cancer cells.Two new citrinin derivatives, pencitrin (1) and pencitrinol (2), and a known compound citrinin (3), together with its two known dimers, penicitrinone A (4), penicitrinone E (5), were isolated from an endophytic fungus P. citrinum 46 derived from Salicornia herbacea Torr. by adding CuCl2 into fermentation medium. The structures of these compounds were elucidated by detailed spectroscopic analysis, and the absolute configurations of 1, 4, and 5 were determined by comparison of quantum chemical time-dependent density functional theory (TDDFT) calculated and electronic circular dichroism (ECD) spectra. Compound 1 exhibited potent cytotoxic activities towards A549 human lung cancer cells and HepG2 human liver cancer cells with IC50 values of 23.73 ± 3.61 and 35.73 ± 2.15 μM, respectively, whereas compound 5 showed moderate cytotoxic activities towards A549 and HepG2 cancer cells with IC50 values of 40.47 ± 4.52 and 53.57 ± 3.24 μM, respectively. The results from the current research highlighted the effectiveness and usefulness of the pipeline to discover novel bioactive fungal secondary metabolites by modification of the culture media.Download high-res image (117KB)Download full-size image

•Polyacetylene glycosides were isolated and identified from Coreopsis tinctoria Nutt.•This is the first report concerning isolation of coreoside E and F from C. tinctoria.•Coreoside E exhibited high levels of the antimicrobial activity.Polyacetylene glycosides, (6Z, 12E)-tetradecadiene-8,10-diyne-1-ol-3(R)-O-β-D-glucopyranoside (trivially named coreoside E) and (6Z, 12E)-tetradecadiene-8,10-diyne-1-ol-3(R)-O-β-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranoside (trivially named coreoside F), were isolated from buds of Coreopsis tinctoria Nutt., together with one known compound, coreoside B. Their chemical structures were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivities. Coreoside E exhibited high levels of antimicrobial activity against Staphylococcus aureus and Bacillus anthracis with minimum inhibitory concentrations of 27 ± 0.27 and 18 ± 0.40 μM, respectively, whereas coreoside F and coreoside B showed weak antimicrobial activity against S. aureus and B. anthracis.Polyacetylene glycosides, with antimicrobial activity against Bacillus anthracis, were isolated from Coreopsis tinctoria Nutt. Their structures were elucidated by spectroscopic analysis and from their chemical reactivity.Download high-res image (148KB)Download full-size image

A phylogeny-guided approach was applied to screen endophytic fungi containing type I polyketide synthase (PKS I) biosynthetic gene sequences and aimed to correlate genotype to chemotype for the discovery of novel bioactive polyketides. Salicorn 58, which was identified as Talaromyces funiculosus based on its internal transcribed spacer (ITS) and ribosomal large-subunit (LSU) DNA sequences, showed significant target bands. A chemical investigation of the culture of Salicorn 58 was allowed for the isolation of a new polyketide, Talafun (1), and a new natural product, N-(2′-hydroxy-3′-octadecenoyl)-9-methyl-4,8-sphingadienin (2), together with six known compounds, including chrodrimanin A (3), chrodrimanin B (4), N-(4-hydroxy-2-methoxyphenyl) acetamide (5), butyl β-glucose (6), 3β,15β-dihydroxyl-(22E, 24R)-ergosta-5,8(14),22-trien-7-dione (7), and (3β,5a,8a,22E)-5,8-epidioxyergosta-6,22-dien-3-ol (8). Their chemical structures were elucidated by extensive spectroscopic analysis and electro circular dichroism (ECD) spectrum calculations. Antioxidant experiments revealed that compound 5 showed strong ABTS+ radical scavenging activity with an IC50 value of 11.43 ± 1.61 μM and potent ferric reducing activity (FRAP assay) with FRAP value of 187.52 ± 2.97. Antimicrobial assays revealed that compounds 1 and 4 showed high levels of selectivity toward Escherichia coli with MIC values of 18 ± 0.40 and 43 ± 0.52 μM, respectively. Compounds 2 and 3 exhibited broad-spectrum antimicrobial activity against Staphylococcus aureus, Mycobacterium smegmatis, Micrococcus tetragenus, Mycobacterium phlei, and E. coli, respectively. The results from the current research highlight the advantage of phylogeny-guided pipeline for the screening of new polyketides from endophytic fungi containing PKS I genes.

•The bound phenolic compounds present in rice bran were released by alkaline hydrolysis.•Para-hydroxy methyl benzoate glucoside was identified in the bound phenolic fraction.•Trans-ferulic acid was the major bound phenolic compound in rice bran with strong antioxidant activity.The bound phenolic compounds in rice bran were released and extracted with ethyl acetate based on alkaline digestion. An investigation of the chemical constituents of EtOAc extract has led to the isolation of a new compound, para-hydroxy methyl benzoate glucoside (8), together with nine known compounds, cycloeucalenol cis-ferulate (1), cycloeucalenol trans-ferulate (2), trans-ferulic acid (3), trans-ferulic acid methyl ester (4), cis-ferulic acid (5), cis-ferulic acid methyl ester (6), methyl caffeate (7), vanillic aldehyde (9) and para-hydroxy benzaldehyde (10). The structures of these compounds were determined using a combination of spectroscopic methods and chemical analysis. Among the compounds isolated, compound 3, 5 and 7 exhibited strong DPPH and ABTS+ radical scavenging activities, followed by compounds 4 and 6. Compound 1 and 2 showed potent DPPH and ABTS+ radical scavenging activities, compound 8 displayed moderate antioxidant activity against ABTS+ radical, whereas compound 9 and 10 showed weak antioxidant activity.

Three new phenolic compounds, coretinphenol (1), coretincone (2), and coretinphencone (3), were isolated from the buds of Coreopsis tinctoria Nutt., together with nine known compounds, including butein (4), okanin (5), isoliquiritigenin (6), maritimetin (7), taxifolin (8), isookanin (9), marein (10), sachalinoside B (11), and 2-phenylethyl-β-d-glucoside (12). The chemical structures of these compounds were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivity. This work represents the first recorded example of the isolation of compounds 1–3, 6, 7, 9, 11, and 12 from C. tinctoria. Compounds 5–9 showed strong diphenyl(2,4,6-trinitrophenyl)iminoazanium (DPPH) radical-scavenging activity, with IC50 values of 3.35 ± 0.45, 9.6 ± 2.32, 4.12 ± 0.21, 6.2 ± 0.43, and 7.9 ± 0.53 μM, respectively. Compounds 2 and 8 exhibited angiotensin I-converting enzyme inhibitory activity, with IC50 values of 228 ± 4.47 and 145.67 ± 3.45 μM, respectively. The activities of phenolic compounds isolated from C. tinctoria support the medicinal use of this plant in the prevention of cardiovascular diseases.

A novel endophytic oleaginous fungus ‘Salicorn 5’ was isolated from Salicornia bigelovii Torr. Morphological characterization and phylogenetic analysis revealed the isolate could be characterized as a new species of the genus Cunninghamella and was subsequently named Cunninghamella bigelovii. The new species was found to accumulate high levels of unsaturated fatty acids, including polyunsaturated fatty acid γ-linolenic acid (GLA) that accounted for 13.28 % of the total fatty acid content by weight.

A large amount of bound compounds, especially phenolics, present in corn bran has been underestimated because of difficulties in extracting them directly by organic solvents under mild conditions. Based on alkaline digestion, the bound compounds in corn bran were released and extracted with ethyl acetate. An investigation of the chemical constituents of the ethyl acetate (EtOAc) extract led to the isolation of ten compounds: trans-ferulic acid (1), trans-ferulic acid methyl ester (2), cis-ferulic acid (3), cis-ferulic acid methyl ester (4), vanillin (5), para-hydroxybenzaldehyde (6), 2-(1-oxo-2-hydroxyethyl) furan (7), graminones B (8), β-sitosterol glucoside (9), and sucrose (10). The chemical structures of these compounds were elucidated mainly by nuclear magnetic resonance and electrospray ionization mass spectrometry analysis. Graminones B was identified for the first time and showed potent angiotensin I-converting enzyme inhibitory activity, and compounds 1, 2, 3, and 4 displayed strong DPPH and ABTS+ radical-scavenging activity. This work represents the first recorded example of the isolation of compounds 3, 4, 8, and 9 from corn bran in the bound form.

An endophytic fungus Salicorn 19 was isolated from Salicornia bigelovii Torr. and identified as Fusarium tricinctum using a combination of translation elongation factor 1 alpha (EF-1α) and β-tubulin (β-TUB) gene sequence analysis. A bioassay-guided fractionation led to a new sesquiterpenoid ether with unique skeleton fusartricin (1), and two known compounds fusarielin B (2) and enniatin B (3) from the culture of Salicorn 19. Their chemical structures were elucidated based on ESI–MS and NMR analysis, as well as a comparison with the literature data. Antimicrobial experiments revealed that compounds 1 exhibited significant antimicrobial activities against E. aerogenes, M. tetragenu and C. albicans with the MIC values 19, 19 and 19 µM, respectively, and compound 2 showed a broader spectrum antimicrobial activity against M. smegmati, B. subtilis, M. phlei and E.coli with MIC values 19, 19, 10 and 10 µM, respectively, and compound 3 displayed powerful antimicrobial activities toward B. subtilis, E. aerogenes and M. tetragenus with MIC values 13, 13 and 6 µM.

•Two new noroleanane-type triterpene saponins have been isolated from S. herbacea.•The first reported isolation of several different compounds from S. herbacea.•These two new compounds, Salbige A and B, showed potent antiproliferative activities.•Pheophorbide a showed powerful antiproliferative activities.•The phytochemicals in S. herbacea work in synergy for its antiproliferative activity.Two new noroleanane-type triterpene saponins, Salbige A (1) and Salbige B (2), have been isolated from the aerial parts of Salicornia herbacea together with five other known compounds, including echinocystic acid (3), gypsogenin (4), pheophorbide a (5), (132S)-hydroxy-pheophorbide a (6) and (132S)-hydro-pheophorbide-lactone a (7). The chemical structures of these compounds were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivity. This work represents the first recorded example of the isolation of these compounds from S. herbacea. Compounds 1 and 2 exhibited potent antiproliferative activities and high levels of selectivity towards A549 cancer cells, with IC50 values of 52.35 and 79.39 μM, respectively, whereas compound 5 showed high levels of inhibitory activity against A549 and HepG2 cancer cells with IC50 values of 6.15 and 17.56 μM, respectively. None of these compounds exhibited antioxidant activities except for compound 7, which showed weak antioxidant activity.

A new screw lactam and two new carbohydrate derivatives, oryzalactam (1), oryzasaccharide A (2), and oryzasaccharide B (3), have been isolated from the methanol extract of rice bran together with four other known compounds, including momilactone A (4), butyl β-d-xylopyranose (5), ethyl β-d-xylopyranose (6), and methyl β-d-xylopyranose (7). The structures of these compounds were determined using a combination of spectroscopic methods and chemical analysis. This work represents the first recorded example of the isolation of compounds 1, 2, 3, 5, 6, and 7 from rice bran. The antioxidant experiments revealed that compound 1 possessed strong ABTS+ (ABTS = 2,2′-azinobis(3-ethylbenzthiazoline-6-sulfonic acid)) and DPPH (DPPH = diphenyl(2,4,6-trinitrophenyl) iminoazanium) radical scavenging with IC50 values of 33.38 ± 1.58 and 40.20 ± 1.34 μM, respectively. Antimicrobial assays revealed that compound 4 showed high levels of selectivity toward Escherichia coli with a minimal inhibitory concentration value of 5 μM.

Salicorn 46, an endophytic fungus isolated from Salicornia herbacea Torr., was identified as Penicillium citrinum based on its internal transcribed spacer and ribosomal large-subunit DNA sequences using a type I polyketide synthase (PKS I) gene screening approach. A new polyketide, penicitriketo (1), and seven known compounds, including ergone (2), (3β,5α,8α,22E)-5,8-epidioxyergosta-6,9,22-trien-3-ol (3), (3β,5α,8α,22E)-5,8-epidioxyergosta-6,22-dien-3-ol (4), stigmasta-7,22-diene-3β,5α,6α-triol (5), 3β,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6β-yl oleate (6), Nb-acetyltryptamine (7), and 2-(1-oxo-2-hydroxyethyl) furan (8), were isolated from the culture of Salicorn 46, and their chemical structures were elucidated by spectroscopic analysis. Antioxidant experiments revealed that compound 1 possessed moderate DPPH radical scavenging activity with an IC50 value of 85.33 ± 1.61 μM. Antimicrobial assays revealed that compound 2 exhibited broad-spectrum antimicrobial activity against Candida albicans, Clostridium perfringens, Mycobacterium smegmatis, and Mycobacterium phlei with minimal inhibitory concentration (MIC) values of 25.5, 25.5, 18.5, and 51.0 μM, respectively. Compound 3 displayed potent antimicrobial activities against C. perfringens and Micrococcus tetragenus with a MIC value of 23.5 μM. Compounds 5 and 6 showed high levels of selectivity toward Bacillus subtilis and M. phlei with MIC values of 22.5 and 14.4 μM, respectively. The results of this study highlight the use of PCR-based techniques for the screening of new polyketides from endophytic fungi containing PKS I genes.

An endophytic fungus Salicorn 8 was isolated from Salicornia bigelovii Torr. and identified as Fusarium equiseti based on internal transcribed spacer gene (ITS) sequence analysis. A new glucitol, diglucotol (1), together with five known compounds, cerebroside C (2), Nb-acetyltryptamine (3), 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (4), cerevisterol (5) and ergosterol peroxide (6), was isolated from the culture of Salicorn 8. The chemical structures of these compounds were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivities. This work describes for the first time the isolation of these compounds from F. equiseti. Compound 1 exhibited weak antiproliferative activities toward MCF-7, MDA-MB-231 and Caco-2 cancer cells with EC50 values of 97.56, 92.35 and 99.39 μM, respectively, whereas compound 5 showed high levels of inhibitory activities against MCF-7, MDA-MB-231 and Caco-2 cancer cells with EC50 values of 32.4, 41.5 and 37.56 μM, respectively. Compound 6 exhibited less potent inhibitory activities than 5 against MCF-7, MDA-MB-231 and Caco-2 cancer cells with EC50 values of 64.5, 52.4 and 77.56 μM, respectively. All of the other compounds were found to be inactive.

An endophytic oleaginous fungus Salicorn 5 has been isolated from Salicornia bigelovii Torr. and characterized as Cunninghamella sp. based on its morphological characteristics and ITS1-5.8S-ITS2 gene sequence analysis. The individual lipid compositions produced by Salicorn 5 were isolated and determined to be (1) oleic acid, (2) linoleic acid, (3) γ-linolenic acid (GLA), (4) 2,3-dihydroxypropyl oleate, (5) 2,3-dihydroxypropyl stearate, (6) 1,3-diolein, (7) 1,2-diolein, (8) 1,3-2-oleyl,2-stearoyl triacylglycerol, (9) ergosterol peroxide, (10) stigmasta-7,22-diene-3β,5α,6α-triol, (11) stigmasterol, and (12) ergosterol. The chemical structures of these compounds were determined by a combination of electrospray ionization mass spectrometry (ESI–MS) and nuclear magnetic resonance (NMR) analysis, as well as a comparison with data from the literature. Analysis of the fatty acids showed that they were composed predominantly of polyunsaturated fatty acids (PUFAs), including oleic acid (35.57 %), linoleic acid (21.58 %), palmitoleic acid (16.31 %), and linolenic acid (13.28 %), whereas stearic acid, palmitoleic acid, myristic acid, arachidic acid, and eicosenoic acid were found in lower amounts. These results could therefore provide a useful platform for fully exploring the potential application of oleaginous fungus Salicorn 5, and optimizing of the fermentation conditions for producing the PUFAs and high-value GLA, as well as providing further insight into the relationship between endophytes and their hosts.

Highlights•One new natural product has been isolated from Salicornia herbacea.•Pentadecyl ferulate exhibited strong antioxidant and potent antitumor activities.•Pentadecyl ferulate was the main antioxidant agent in the S. herbacea extracts.•Several phytochemicals were responsible for the antioxidant activity of S. herbacea.An investigation of the chemical constituents of Salicornia herbacea has led to the isolation of one new natural product, pentadecyl ferulate (6), together with 11 known compounds, including phytol (1), stearolic acid (2), γ-linolenic acid (3), (3Z,6Z,9Z)-tricosa-3,6,9-triene (4), linoleic acid (5), stigmasterol (7), ergosterol (8), dioctyl phthalate (9), dibutyl phthalate (10), vanillic aldehyde (11), and scopoletin (12). The chemical structures of these materials were elucidated mainly by spectroscopic analysis. This work represents the first recorded example of the isolation of compounds 1, 2, 3, 4, 9, 10, and 11 from S. herbacea. The antioxidant experiments revealed that compound 6 possessed strong hydroxy radical and superoxide anion scavenging activities and was the principle antioxidant ingredient in the ethyl acetate extract. The antiproliferative results exhibited that compound 1 selectively inhibited HepG2 cells, whereas compounds 3 and 6 showed potent antiproliferative activities against HepG2 and A549 cells.

Six new indole alkaloids including five new glyantrypine derivatives (1, 2a, 2b, 3, 4) and a new pyrazinoquinazoline derivative (5), together with eight known alkaloids (6–13), were isolated from the culture of the mangrove-derived fungus Cladosporium sp. PJX-41. Their structures were elucidated primarily by spectroscopic and physical data. The absolute configurations of compounds 1–9 were established on the basis of CD, NOESY data, and single-crystal X-ray diffraction analysis. Compounds 2b, 5, 7–9, and 11 exhibited significant activities against influenza virus A (H1N1), with IC50 values of 82–89 μM.