Marine Drugs

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13 pages, 830 KiB

Open AccessArticle

Cryptic Secondary Metabolites from the Sponge-Associated Fungus Aspergillus ochraceus

by Marian Frank, Ferhat Can Özkaya, Werner E. G. Müller, Alexandra Hamacher, Matthias U. Kassack, Wenhan Lin, Zhen Liu and Peter Proksch

Mar. Drugs 2019, 17(2), 99; https://doi.org/10.3390/md17020099 - 3 Feb 2019

Cited by 35 | Viewed by 5101

Abstract

The fungus Aspergillus ochraceus was isolated from the Mediterranean sponge Agelas oroides. The initial fermentation of the fungus on solid rice medium yielded 16 known compounds (4–19). The addition of several inorganic salts to the rice medium mainly [...] Read more.

The fungus Aspergillus ochraceus was isolated from the Mediterranean sponge Agelas oroides. The initial fermentation of the fungus on solid rice medium yielded 16 known compounds (4–19). The addition of several inorganic salts to the rice medium mainly influenced the accumulation of these secondary metabolites. Fermentation of the fungus on white bean medium yielded the new waspergillamide B (1) featuring an unusual p-nitrobenzoic acid as partial structure. Moreover, two new compounds, ochraspergillic acids A and B (2 and 3), which are both adducts of dihydropenicillic acid and o- or p-aminobenzoic acid, were isolated from the co-culture of the fungus with Bacillus subtilis. Compound 2 was also detected in axenic fungal cultures following the addition of either anthranilic acid or tryptophan to the rice medium. The structures of the new compounds were established by 1D and 2DNMR experiments as well as from the HRMS data. The absolute configuration of 1 was elucidated following hydrolysis and derivatization of the amino acids using Marfey’s reagent. Viomellein (9) and ochratoxin B (18) exhibited strong cytotoxicity against the A2780 human ovarian carcinoma cells with IC₅₀ values of 5.0 and 3.0 µM, respectively. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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14 pages, 3753 KiB

Open AccessArticle

Isolation and Absolute Configurations of Diversiform C₁₇, C₂₁ and C₂₅ Terpenoids from the Marine Sponge Cacospongia sp.

by Xingwang Zhang, Ping-Lin Li, Guo-Fei Qin, Shengying Li, Nicole J. De Voogd, Xu-Li Tang and Guo-Qiang Li

Mar. Drugs 2019, 17(1), 14; https://doi.org/10.3390/md17010014 - 28 Dec 2018

Cited by 10 | Viewed by 4072

Abstract

Chemical investigation of MeOH extract of a South China Sea sponge Cacospongia sp. yielded 15 terpenoids belonging to three different skeleton-types, including the unusual C₁₇ γ-lactone norditerpenoids (1–3), the rare C₂₁ pyridine meroterpenoid (7), [...] Read more.

Chemical investigation of MeOH extract of a South China Sea sponge Cacospongia sp. yielded 15 terpenoids belonging to three different skeleton-types, including the unusual C₁₇ γ-lactone norditerpenoids (1–3), the rare C₂₁ pyridine meroterpenoid (7), and the notable C₂₅ manoalide-type sesterterpenoids (4–6, 8–10). Compounds 1–5 were initially obtained as enantiomers, and were further separated to be optically pure compounds (1a, 1b, 2a, 2b, 3a-r, 3b-r, 4a, 4b, 5a and 5b) by chiral HPLC, with a LiAlH₄ reduction aid for 3. Compounds 3a/3b (a pair of inseparable enantiomers), 4a, 5a, 6, and 7 were identified as new compounds, while 1a/1b and 2a/2b were obtained from a natural source and were determined for their absolute configurations for the first time. This is also the first time to encounter enantiomers of the well-known manoalide-type sesterterpenoids from nature. The structures with absolute configurations of the new compounds were unambiguously determined by comprehensive methods including HR-ESI-MS and NMR data analysis, optical rotation comparison, experimental and calculated electronic circular dichroism (ECD), and Mo₂(OAc)₄ induced circular dichroism (ICD) methods. The cytotoxicity of the isolates against selected human tumor cell lines was evaluated, however, the tested compounds showed no activity against selected cell lines. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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12 pages, 3402 KiB

Open AccessCommunication

Diketopiperazine and Diphenylether Derivatives from Marine Algae-Derived Aspergillus versicolor OUCMDZ-2738 by Epigenetic Activation

by Wen Liu, Liping Wang, Bin Wang, Yanchao Xu, Guoliang Zhu, Mengmeng Lan, Weiming Zhu and Kunlai Sun

Mar. Drugs 2019, 17(1), 6; https://doi.org/10.3390/md17010006 - 22 Dec 2018

Cited by 42 | Viewed by 4810

Abstract

A chemical-epigenetic method was used to enhance the chemodiversity of a marine algicolous fungus. Apart from thirteen known compounds, (+)-brevianamide R ((+)-3), (‒)-brevianamide R ((‒)-3), (+)-brevianamide Q ((+)-4), (‒)-brevianamide Q ((‒)-4), brevianamide V ((+)-5 [...] Read more.

A chemical-epigenetic method was used to enhance the chemodiversity of a marine algicolous fungus. Apart from thirteen known compounds, (+)-brevianamide R ((+)-3), (‒)-brevianamide R ((‒)-3), (+)-brevianamide Q ((+)-4), (‒)-brevianamide Q ((‒)-4), brevianamide V ((+)-5), brevianamide W ((‒)-5), brevianamide K (6), diorcinol B (7), diorcinol C (8), diorcinol E (9), diorcinol J (10), diorcinol (11), 4-methoxycarbonyldiorcinol (12), two new compounds, (+)- and (‒)-brevianamide X ((+)- and (‒)- 2)), as well as a new naturally occurring one, 3-[6-(2-methylpropyl)-2-oxo-1H-pyrazin-3-yl]propanamide (1), were isolated from chemical-epigenetic cultures of Aspergillus versicolor OUCMDZ-2738 with 10 µM vorinostat (SAHA). Compared to cultures in the same medium without SAHA, compounds 1–4, 8, 9, 11, and 12 were solely observed under SAHA condition. The structures of these compounds were elucidated based on spectroscopic analysis, specific rotation analysis, ECD, and X-ray crystallographic analysis. (±)-3, (±)-4, and (±)-5 were further resolved into the corresponding optically pure enantiomers and their absolute configurations were determined for the first time. Compounds 11 and 12 showed selective antibacterial against Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 17.4 and 13.9 μM, respectively. Compound 10 exhibited better α-glucosidase inhibitory activity than the assay control acarbose with IC₅₀ values of 117.3 and 255.3 μM, respectively. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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11 pages, 667 KiB

Open AccessArticle

Diphenyl Ethers from a Marine-Derived Aspergillus sydowii

by Ya-Nan Wang, Yan-Hua Mou, Yu Dong, Yan Wu, Bing-Yu Liu, Jian Bai, Dao-Jiang Yan, Le Zhang, Dan-Qing Feng, Yue-Hu Pei and You-Cai Hu

Mar. Drugs 2018, 16(11), 451; https://doi.org/10.3390/md16110451 - 16 Nov 2018

Cited by 28 | Viewed by 4380

Abstract

Six new diphenyl ethers (1–6) along with eleven known analogs were isolated from the ethyl acetate extract of a marine-derived Aspergillus sydowii guided by LC-UV-MS. Their structures were unambiguously characterized by HRESIMS, NMR, as well as chemical derivatization. Compounds [...] Read more.

Six new diphenyl ethers (1–6) along with eleven known analogs were isolated from the ethyl acetate extract of a marine-derived Aspergillus sydowii guided by LC-UV-MS. Their structures were unambiguously characterized by HRESIMS, NMR, as well as chemical derivatization. Compounds 1 and 2 are rare diphenyl ether glycosides containing d-ribose. The absolute configuration of the sugar moieties in compounds 1–3 was determined by a LC-MS method. All the compounds were evaluated for their cytotoxicities against eight cancer cell lines, including 4T1, U937, PC3, HL-60, HT-29, A549, NCI-H460, and K562, and compounds 1, 5, 6, and 8–11 were found to exhibit selective cytotoxicity against different cancer cell lines. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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9 pages, 615 KiB

Open AccessArticle

Potential Antiviral Xanthones from a Coastal Saline Soil Fungus Aspergillus iizukae

by Hui-Hui Kang, Huai-Bin Zhang, Mei-Jia Zhong, Li-Ying Ma, De-Sheng Liu, Wei-Zhong Liu and Hong Ren

Mar. Drugs 2018, 16(11), 449; https://doi.org/10.3390/md16110449 - 15 Nov 2018

Cited by 31 | Viewed by 4445

Abstract

Five new (1–5) and two known xanthones (6 and 7), one of the latter (6) obtained for the first time as a natural product, together with three known anthraquinones, questin, penipurdin A, and questinol, were [...] Read more.

Five new (1–5) and two known xanthones (6 and 7), one of the latter (6) obtained for the first time as a natural product, together with three known anthraquinones, questin, penipurdin A, and questinol, were isolated from the coastal saline soil-derived Aspergillus iizukae by application of an OSMAC (one strain many compounds) approach. Their structures were determined by interpretation of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, as well as comparison of these data with those of related known compounds. Antiviral activity of xanthones 1−7 was evaluated through the cytopathic effect (CPE) inhibition assay, and compound 2 exhibited distinctly strong activity towards influenza virus (H1N1), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) with IC₅₀ values of 44.6, 21.4, and 76.7 μM, respectively, which indicated that it was worth to further investigate it as a potential lead compound. The preliminary structure-activity relationship of the xanthones is discussed. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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8 pages, 1266 KiB

Open AccessArticle

Anthracimycin B, a Potent Antibiotic against Gram-Positive Bacteria Isolated from Cultures of the Deep-Sea Actinomycete Streptomyces cyaneofuscatus M-169

by Víctor Rodríguez, Jesús Martín, Aida Sarmiento-Vizcaíno, Mercedes De la Cruz, Luis A. García, Gloria Blanco and Fernando Reyes

Mar. Drugs 2018, 16(11), 406; https://doi.org/10.3390/md16110406 - 25 Oct 2018

Cited by 38 | Viewed by 6552

Abstract

The potent antimicrobial extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-169 was fractionated by reversed phase flash chromatography and preparative HPLC to yield the new Gram-positive antibiotic, anthracimycin B (1), together with its congener, anthracimycin (2 [...] Read more.

The potent antimicrobial extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-169 was fractionated by reversed phase flash chromatography and preparative HPLC to yield the new Gram-positive antibiotic, anthracimycin B (1), together with its congener, anthracimycin (2). The structure of the new compound was established by analysis of its ESI-TOF MS and 1D and 2D NMR spectra, and comparison with data published for anthracimycin and anthracimycin BII-2619 (3). Notably, anthracimycin seemed to be the major and almost unique component of the extract detected by HPLC-UV-MS, making our S. cyanofuscatus strain an excellent candidate for further biosynthetic studies of this potent antibiotic. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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11 pages, 1313 KiB

Open AccessArticle

New 3-Hydroxyquinaldic Acid Derivatives from Cultures of the Marine Derived Actinomycete Streptomyces cyaneofuscatus M-157

by Francisco Javier Ortiz-López, Elsa Alcalde, Aida Sarmiento-Vizcaíno, Caridad Díaz, Bastien Cautain, Luis A. García, Gloria Blanco and Fernando Reyes

Mar. Drugs 2018, 16(10), 371; https://doi.org/10.3390/md16100371 - 8 Oct 2018

Cited by 23 | Viewed by 5168

Abstract

Fractionation of the bioactive extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-157 led to the isolation of the known 3-hydroxyquinaldic acid (4), its amide (5) and three new derivatives (1–3) containing [...] Read more.

Fractionation of the bioactive extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-157 led to the isolation of the known 3-hydroxyquinaldic acid (4), its amide (5) and three new derivatives (1–3) containing different amino acid residues. The structures of the new molecules (1–3), including their absolute configuration, were determined by the analysis of their ESI-TOF MS and one-dimensional (1D) and two-dimensional (2D) NMR spectra and advanced Marfey’s analysis of their hydrolyzation products. Compound 3 spontaneously dimerized in solution to give the disulfide derivative 6. Unfortunately, none of the new compounds isolated confirmed the antimicrobial activity found in the bacterial extract, perhaps indicating that such antibacterial activity might be due to presence in the extract at the trace level of larger bioactive 3-hydroxyquinaldic acid derivatives from which compounds 1–3 are biosynthetic precursors. Cytotoxicity tests confirmed the moderate and weak IC₅₀ values of 15.6 and 51.5 µM for compounds 5 and 1, respectively. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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8 pages, 987 KiB

Open AccessArticle

Aspergixanthones I–K, New Anti-Vibrio Prenylxanthones from the Marine-Derived Fungus Aspergillus sp. ZA-01

by Ao Zhu, Xing-Wang Zhang, Miao Zhang, Wan Li, Zheng-Yue Ma, Hua-Jie Zhu and Fei Cao

Mar. Drugs 2018, 16(9), 312; https://doi.org/10.3390/md16090312 - 4 Sep 2018

Cited by 30 | Viewed by 4542

Abstract

Marine-derived fungi are a rich source of structurally diverse metabolites. Fungi produce an array of compounds when grown under different cultivation conditions. In the present work, different media were used to cultivate the fungus Aspergillus sp. ZA-01, which was previously studied for the [...] Read more.

Marine-derived fungi are a rich source of structurally diverse metabolites. Fungi produce an array of compounds when grown under different cultivation conditions. In the present work, different media were used to cultivate the fungus Aspergillus sp. ZA-01, which was previously studied for the production of bioactive compounds, and three new prenylxanthone derivatives, aspergixanthones I–K (1–3), and four known analogues (4–7) were obtained. The absolute configuration of 1 was assigned by ECD experiment and the Mo₂(AcO)₄ ICD spectrum of its methanolysis derivative (1a). All the compounds (1–7) were evaluated for their anti-Vibrio activities. Aspergixanthone I (1) showed the strongest anti-Vibrio activity against Vibrio parahemolyticus (MIC = 1.56 μM), Vibrio anguillarum (MIC = 1.56 μM), and Vibrio alginolyticus (MIC = 3.12 μM). Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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11 pages, 2622 KiB

Open AccessArticle

Innovative Approach to Sustainable Marine Invertebrate Chemistry and a Scale-Up Technology for Open Marine Ecosystems

by Pinelopi Vlachou, Géraldine Le Goff, Carolina Alonso, Pedro A. Álvarez, Jean-François Gallard, Nikolas Fokialakis and Jamal Ouazzani

Mar. Drugs 2018, 16(5), 152; https://doi.org/10.3390/md16050152 - 6 May 2018

Cited by 14 | Viewed by 6971

Abstract

Isolation of marine compounds from living invertebrates represents a major challenge for sustainable and environmentally friendly exploitation of marine bio-resources. To develop innovative technology to trap invertebrate compounds in the open sea, the proof of concept of a system combining external continuous circulation [...] Read more.

Isolation of marine compounds from living invertebrates represents a major challenge for sustainable and environmentally friendly exploitation of marine bio-resources. To develop innovative technology to trap invertebrate compounds in the open sea, the proof of concept of a system combining external continuous circulation of water with XAD-amberlite solid-phase extraction was validated in an aquarium. In this work, we reported the elicitation of guanidine alkaloid production of Crambe crambe in the presence of Anemonia sulcata, both collected from the Mediterranean Sea. Besides the previously reported crambescidin 359 (1), and crambescidin acid (2), three new compounds were isolated; one carboxylated analog of 1 named crambescidin 401 (3), and two analogs of crambescin B, crambescin B 281 (4) and crambescin B 253 (5). Based on these results, a technology named Somartex^® for “Self Operating MARine Trapping Extractor” was patented and built to transfer the concept from closed aquarium systems to open marine ecosystems. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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13 pages, 2540 KiB

Open AccessFeature PaperArticle

Phocoenamicins B and C, New Antibacterial Spirotetronates Isolated from a Marine Micromonospora sp.

by Mercedes Pérez-Bonilla, Daniel Oves-Costales, Mercedes De la Cruz, Maria Kokkini, Jesús Martín, Francisca Vicente, Olga Genilloud and Fernando Reyes

Mar. Drugs 2018, 16(3), 95; https://doi.org/10.3390/md16030095 - 16 Mar 2018

Cited by 31 | Viewed by 6414

Abstract

Phocoenamicins B and C (1 and 2), together with the known spirotetronate phocoenamicin (3), were isolated from cultures of Micromonospora sp. The acetone extract from a culture of this strain, isolated from marine sediments collected in the Canary Islands, [...] Read more.

Phocoenamicins B and C (1 and 2), together with the known spirotetronate phocoenamicin (3), were isolated from cultures of Micromonospora sp. The acetone extract from a culture of this strain, isolated from marine sediments collected in the Canary Islands, displayed activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis H37Ra and Mycobacterium bovis. Bioassay-guided fractionation of this extract using SP207ss column chromatography and preparative reversed-phased HPLC led to the isolation of the new compounds 1 and 2 belonging to the spirotetronate class of polyketides. Their structures were determined using a combination of HRMS, 1D and 2D NMR experiments and comparison with the spectra reported for phocoenamicin. Antibacterial activity tests of the pure compounds against these pathogens revealed minimal inhibitory concentration (MIC) values ranging from 4 to 64 µg/mL for MRSA, and 16 to 32 µg/mL for M. tuberculosis H37Ra, with no significant activity found against M. bovis and vancomycin-resistant Enterococcus faecium (VRE) at concentrations below 128 µg/mL, and weak activity detected against Bacillus subtilis grown on agar plates. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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10 pages, 763 KiB

Open AccessArticle

Ecdysonelactones, Ecdysteroids from the Tropical Eastern Pacific Zoantharian Antipathozoanthus hickmani

by Paul O. Guillen, Kevin Calabro, Karla B. Jaramillo, Cristobal Dominguez, Grégory Genta-Jouve, Jenny Rodriguez and Olivier P. Thomas

Mar. Drugs 2018, 16(2), 58; https://doi.org/10.3390/md16020058 - 11 Feb 2018

Cited by 8 | Viewed by 5010

Abstract

Despite a large occurrence, especially over the Pacific Ocean, the chemical diversity of marine invertebrates belonging to the order Zoantharia is largely underexplored. For the two species of the genus Antipathozoanthus no chemical study has been reported so far. The first chemical investigation [...] Read more.

Despite a large occurrence, especially over the Pacific Ocean, the chemical diversity of marine invertebrates belonging to the order Zoantharia is largely underexplored. For the two species of the genus Antipathozoanthus no chemical study has been reported so far. The first chemical investigation of Antipathozoanthus hickmani collected at the Marine Protected Area “El Pelado”, Santa Elena, Ecuador, led to the isolation of four new ecdysteroid derivatives named ecdysonelactones. The structures of ecdysonelactones A–D (1–4) were determined based on their spectroscopy data, including 1D and 2D NMR and HRMS. The four compounds of this family of ecdysteroids feature an unprecedented γ-lactone fused at the C-2/C-3 position of ring A. These derivatives exhibited neither antimicrobial nor cytotoxic activities. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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13 pages, 2377 KiB

Open AccessArticle

Identification, Characteristics and Mechanism of 1-Deoxy-N-acetylglucosamine from Deep-Sea Virgibacillus dokdonensis MCCC 1A00493

by Dian Huang, Zong-Ze Shao, Yi Yu, Min-Min Cai, Long-Yu Zheng, Guang-Yu Li, Zi-Niu Yu, Xian-Feng Yi, Ji-Bin Zhang and Fu-Hua Hao

Mar. Drugs 2018, 16(2), 52; https://doi.org/10.3390/md16020052 - 7 Feb 2018

Cited by 8 | Viewed by 5628

Abstract

Xanthomonas oryzae pv. oryzae, which causes rice bacterial blight, is one of the most destructive pathogenic bacteria. Biological control against plant pathogens has recently received increasing interest. 1-Deoxy-N-acetylglucosamine (1-DGlcNAc) was extracted from the supernatant of Virgibacillus dokdonensis MCCC 1A00493 fermentation [...] Read more.

Xanthomonas oryzae pv. oryzae, which causes rice bacterial blight, is one of the most destructive pathogenic bacteria. Biological control against plant pathogens has recently received increasing interest. 1-Deoxy-N-acetylglucosamine (1-DGlcNAc) was extracted from the supernatant of Virgibacillus dokdonensis MCCC 1A00493 fermentation through antibacterial bioassay-guided isolation. Its structure was elucidated by LC/MS, NMR, chemical synthesis and time-dependent density functional theory (TD-DFT) calculations. 1-DGlcNAc specifically suppressed X. oryzae pv. oryzae PXO99A (MIC was 23.90 μg/mL), but not other common pathogens including Xanthomonas campestris pv. campestris str.8004 and Xanthomonas oryzae pv. oryzicola RS105. However, its diastereomer (2-acetamido-1,5-anhydro-2-deoxy-d-mannitol) also has no activity to X. oryzae pv. oryzae. This result suggested that activity of 1-DGlcNAc was related to the difference in the spatial conformation of the 2-acetamido moiety, which might be attributed to their different interactions with a receptor. Eighty-four unique proteins were found in X. oryzae pv. oryzae PXO99A compared with the genome of strains8004 and RS105 by blastp. There may be unique interactions between 1-DGlcNAc and one or more of these unique proteins in X. oryzae pv. oryzae. Quantitative real-time PCR and the pharmMapper server indicated that proteins involved in cell division could be the targets in PXO99A. This research suggested that specificity of active substance was based on the active group and spatial conformation selection, and these unique proteins could help to reveal the specific mechanism of action of 1-DGlcNAc against PXO99A. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)

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