Marine Drugs

Research

10 pages, 2160 KiB

Open AccessArticle

¹H NMR-Based Isolation of Anti-Inflammatory 9,11-Secosteroids from the Octocoral Sinularia leptoclados

by Yu-Chia Chang, Kuei-Hung Lai, Sunil Kumar, Po-Jen Chen, Yi-Hsuan Wu, Ching-Long Lai, Hsi-Lung Hsieh, Ping-Jyun Sung and Tsong-Long Hwang

Mar. Drugs 2020, 18(5), 271; https://doi.org/10.3390/md18050271 - 21 May 2020

Cited by 13 | Viewed by 2632

Abstract

Octocoral Sinularia leptoclados has been identified as a source of bioactive 9,11-secosteroids. This study adopted a targeted isolation approach to the discovery and analysis of five 9,11-secosteroids, including two novel compounds named sinleptosterols A (1) and B (2) as [...] Read more.

Octocoral Sinularia leptoclados has been identified as a source of bioactive 9,11-secosteroids. This study adopted a targeted isolation approach to the discovery and analysis of five 9,11-secosteroids, including two novel compounds named sinleptosterols A (1) and B (2) as well as five known analogues (8αH-3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9-one (3), 8βH-3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9-one (4), leptosterol A (5), (24S)-3β,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9-one (6), and 3β,11-dihydroxy-9,11-secogorgost-5-en-9-one (7)) in terms of ¹H-NMR patterns and potency against neutrophilic inflammation. The structure of secosteroids 1 and 2 was deduced from general spectroscopic analysis and an examination of NMR spectra. Among the above-mentioned isolates, compound 4 had the most pronounced effect in inhibiting elastase release and superoxide anion generation, with the IC₅₀ values of 2.96 and 1.63 μM, respectively. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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14 pages, 2465 KiB

Open AccessArticle

LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4

by Fedor Kryuchkov, Alison Robertson, Christopher O. Miles, Elizabeth M. Mudge and Silvio Uhlig

Mar. Drugs 2020, 18(4), 182; https://doi.org/10.3390/md18040182 - 31 Mar 2020

Cited by 32 | Viewed by 3285

Abstract

Ciguatera poisoning is linked to the ingestion of seafood that is contaminated with ciguatoxins (CTXs). The structural variability of these polyether toxins in nature remains poorly understood due to the low concentrations present even in highly toxic fish, which makes isolation and chemical [...] Read more.

Ciguatera poisoning is linked to the ingestion of seafood that is contaminated with ciguatoxins (CTXs). The structural variability of these polyether toxins in nature remains poorly understood due to the low concentrations present even in highly toxic fish, which makes isolation and chemical characterization difficult. We studied the mass spectrometric fragmentation of Caribbean CTXs, i.e., the epimers C-CTX-1 and -2 (1 and 2), using a sensitive UHPLC–HRMS/MS approach in order to identify product ions of diagnostic value. We found that the fragmentation of the ladder-frame backbone follows a characteristic pattern and propose a generalized nomenclature for the ions formed. These data were applied to the structural characterization of a pair of so far poorly characterized isomers, C-CTX-3 and -4 (3 and 4), which we found to be reduced at C-56 relative to 1 and 2. Furthermore, we tested and applied reduction and oxidation reactions, monitored by LC–HRMS, in order to confirm the structures of 3 and 4. Reduction of 1 and 2 with NaBH₄ afforded 3 and 4, thereby unambiguously confirming the identities of 3 and 4. In summary, this work provides a foundation for mass spectrometry-based characterization of new C-CTXs, including a suite of simple chemical reactions to assist the examination of structural modifications. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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15 pages, 1438 KiB

Open AccessArticle

Polyketide Derivatives from Mangrove Derived Endophytic Fungus Pseudopestalotiopsis theae

by Xiaoqin Yu, Werner E. G. Müller, Dieter Meier, Rainer Kalscheuer, Zhiyong Guo, Kun Zou, Blessing O. Umeokoli, Zhen Liu and Peter Proksch

Mar. Drugs 2020, 18(2), 129; https://doi.org/10.3390/md18020129 - 23 Feb 2020

Cited by 23 | Viewed by 3755

Abstract

Chemical investigation of secondary metabolites from the endophytic fungus Pseudopestalotiopsis theae led to the isolation of eighteen new polyketide derivatives, pestalotheols I–Q (1–9) and cytosporins O–W (15–23), together with eight known analogs (10– [...] Read more.

Chemical investigation of secondary metabolites from the endophytic fungus Pseudopestalotiopsis theae led to the isolation of eighteen new polyketide derivatives, pestalotheols I–Q (1–9) and cytosporins O–W (15–23), together with eight known analogs (10–14 and 24–26). The structures of the new compounds were elucidated by HRMS and 1D and 2D NMR data, as well as by comparison with literature data. Modified Mosher’s method was applied to determine the absolute configuration of some compounds. Compound 23 showed significant cytotoxicity against the mouse lymphoma cell line L5178Y with an IC₅₀ value of 3.0 μM. Furthermore, compounds 22 and 23 showed moderate antibacterial activity against drug-resistant Acinetobacter baumannii (ATCC BAA-1605) in combination with sublethal colistin concentrations. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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13 pages, 1735 KiB

Open AccessArticle

Monarubins A–C from the Marine Shellfish-Associated Fungus Monascus ruber BB5

by Yan-Qin Ran, Wen-Jian Lan, Yi Qiu, Qi Guo, Gong-Kan Feng, Rong Deng, Xiao-Feng Zhu, Hou-Jin Li and Jun Dong

Mar. Drugs 2020, 18(2), 100; https://doi.org/10.3390/md18020100 - 03 Feb 2020

Cited by 8 | Viewed by 2947

Abstract

Three new compounds, monarubins A–C (1, 6 and 13), together with ten known compounds, including four alkaloids (2–5), two isocoumarins (7 and 8) and four polyketides (9–12), were isolated from [...] Read more.

Three new compounds, monarubins A–C (1, 6 and 13), together with ten known compounds, including four alkaloids (2–5), two isocoumarins (7 and 8) and four polyketides (9–12), were isolated from marine shellfish-associated fungus Monascus ruber BB5. The structures were determined on the basis of the 1D and 2D NMR, MS, UV and IR data. The absolute configurations of compounds 3, 6 and 13 were determined by ECD calculations. The NMR data of compounds deoxyhydroxyaspergillic acid (3) and 2-hydroxy-6-(1-hydroxy-1-methylpropyl)-3-sec-buthylpyrazine (4) were first reported. All of the isolated compounds were evaluated for their cytotoxic activities against human nasopharyngeal carcinoma cell lines CNE1, CNE2, SUNE1 and HONE1 and hepatocellular carcinoma cell lines QGY7701 and HepG2. Monarubin B (6) displayed potent cytotoxicities against the cancer cell lines HepG2 and QGY7701 with IC₅₀ values of 1.72 and 0.71 μΜ, respectively; lunatinin (7) showed moderate cytotoxic activities against the cancer cell lines HepG2, QGY7701 and SUNE1 with the IC₅₀ values of 9.60, 7.12 and 28.12 μΜ, respectively. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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9 pages, 1472 KiB

Open AccessArticle

Four New Insecticidal Xanthene Derivatives from the Mangrove-Derived Fungus Penicillium sp. JY246

by Meng Bai, Cai-Juan Zheng, Xu-Hua Nong, Xue-Ming Zhou, You-Ping Luo and Guang-Ying Chen

Mar. Drugs 2019, 17(12), 649; https://doi.org/10.3390/md17120649 - 20 Nov 2019

Cited by 23 | Viewed by 2508

Abstract

Four new xanthene derivatives, penicixanthenes A–D (1–4), and one known compound 5 were isolated from a marine mangrove endophytic fungus Penicillium sp. JY246 that was obtained from the stem of Ceriops tagal. Their structures were determined by detailed [...] Read more.

Four new xanthene derivatives, penicixanthenes A–D (1–4), and one known compound 5 were isolated from a marine mangrove endophytic fungus Penicillium sp. JY246 that was obtained from the stem of Ceriops tagal. Their structures were determined by detailed NMR, MS spectroscopic data, modified Mosher’s method, and calculated electronic circular dichroism data. All of the isolated compounds were examined for insecticidal activity. Compounds 2 and 3 showed growth inhibition activity against newly hatched larvae of Helicoverpa armigera Hubner with the IC₅₀ values 100 and 200 μg/mL, respectively, and compounds 1, 3, and 4 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with LC₅₀ values of 38.5 (±1.16), 11.6 (±0.58), and 20.5 (±1) μg/mL, respectively. The four xanthene derivatives have the potential to be developed as new biopesticides. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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22 pages, 2207 KiB

Open AccessArticle

Novel Microcystins from Planktothrix prolifica NIVA-CYA 544 Identified by LC-MS/MS, Functional Group Derivatization and ¹⁵N-labeling

by Vittoria Mallia, Silvio Uhlig, Cheryl Rafuse, Juris Meija and Christopher O. Miles

Mar. Drugs 2019, 17(11), 643; https://doi.org/10.3390/md17110643 - 15 Nov 2019

Cited by 16 | Viewed by 4245

Abstract

Microcystins are cyclic heptapeptides from cyanobacteria that are potent inhibitors of protein phosphatases and are toxic to animals and humans. At present, more than 250 microcystin variants are known, with variants reported for all seven peptide moieties. While d-glutamic acid (d [...] Read more.

Microcystins are cyclic heptapeptides from cyanobacteria that are potent inhibitors of protein phosphatases and are toxic to animals and humans. At present, more than 250 microcystin variants are known, with variants reported for all seven peptide moieties. While d-glutamic acid (d-Glu) is highly-conserved at position-6 of microcystins, there has been only one report of a cyanobacterium (Anabaena) producing microcystins containing l-Glu at the variable 2- and 4-positions. Liquid chromatography–mass spectrometry analyses of extracts from Planktothrix prolifica NIVA-CYA 544 led to the tentative identification of two new Glu-containing microcystins, [d-Asp³]MC-ER (12) and [d-Asp³]MC-EE (13). Structure determination was aided by thiol derivatization of the Mdha⁷-moiety and esterification of the carboxylic acid groups, while ¹⁵N-labeling of the culture and isotopic profile analysis assisted the determination of the number of nitrogen atoms present and the elemental composition of molecular and product-ions. The major microcystin analog in the extracts was [d-Asp³]MC-RR (1). A microcystin with an unprecedented high-molecular-mass (2116 Da) was also detected and tentatively identified as a sulfide-linked conjugate of [d-Asp³]MC-RR (15) by LC–HRMS/MS and sulfide oxidation, together with its sulfoxide (16) produced via autoxidation. Low levels of [d-Asp³]MC-RW (14), [d-Asp³]MC-LR (4), [d-Asp³,Mser⁷]MC-RR (11), [d-Asp³]MC-RY (17), [d-Asp³]MC-RF (18), [d-Asp³]MC-RR–glutathione conjugate (19), and [d-Asp³]MC-RCit (20), the first reported microcystin containing citrulline, were also identified in the extract, and an oxidized derivative of [d-Asp³]MC-RR and the cysteine conjugate of 1 were partially characterized. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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9 pages, 944 KiB

Open AccessArticle

Prenylated Phenol and Benzofuran Derivatives from Aspergillus terreus EN-539, an Endophytic Fungus Derived from Marine Red Alga Laurencia okamurai

by Hong-Lei Li, Xiao-Ming Li, Sui-Qun Yang, Ling-Hong Meng, Xin Li and Bin-Gui Wang

Mar. Drugs 2019, 17(11), 605; https://doi.org/10.3390/md17110605 - 24 Oct 2019

Cited by 15 | Viewed by 2633

Abstract

Three new prenylated phenol derivatives, terreprenphenols A–C (1–3), along with four known related compounds (4–7), were isolated from Aspergillus terreus EN-539, an endophytic fungus obtained from the marine red alga Laurencia okamurai. The structures [...] Read more.

Three new prenylated phenol derivatives, terreprenphenols A–C (1–3), along with four known related compounds (4–7), were isolated from Aspergillus terreus EN-539, an endophytic fungus obtained from the marine red alga Laurencia okamurai. The structures of these compounds were established by extensive analysis of 1D/2D NMR data, mass spectrometric data, and optical rotation (OR). The corresponding relationship between absolute configuration and optical rotation for known compounds anodendroic acid (4) and asperterreusine C (5) was ambiguous in literature, and their absolute configurations were therefore discussed and confirmed for the first time by time-dependent density functional (TDDFT) ECD and OR calculations. Compounds 1–7 inhibited some common aquatic bacteria with MIC values ranging from 2 to 64 μg/mL. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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14 pages, 3784 KiB

Open AccessArticle

Bioactive Diketopiperazines and Nucleoside Derivatives from a Sponge-Derived Streptomyces Species

by Lamiaa A. Shaala, Diaa T. A. Youssef, Jihan M. Badr, Steve M. Harakeh and Grégory Genta-Jouve

Mar. Drugs 2019, 17(10), 584; https://doi.org/10.3390/md17100584 - 16 Oct 2019

Cited by 19 | Viewed by 3099

Abstract

Fractionation and purification of the ethyl acetate extract of the culture of a sponge-derived actinomycete, Streptomyces species Call-36, resulted in the isolation and identification of a new diketopiperazine, actinozine A (1), cyclo(2-OH-d-Pro-l-Leu) (2), two new [...] Read more.

Fractionation and purification of the ethyl acetate extract of the culture of a sponge-derived actinomycete, Streptomyces species Call-36, resulted in the isolation and identification of a new diketopiperazine, actinozine A (1), cyclo(2-OH-d-Pro-l-Leu) (2), two new nucleosides, thymidine-3-mercaptocarbamic acid (3) and thymidine-3-thioamine (4), together with cyclo(d-Pro-l-Phe) (5) and cyclo(l-Pro-l-Phe) (6). The structure assignments of the compounds were carried out by interpretation of 1D and 2D NMR data and mass spectral determinations. The absolute configurations of 1 and 2 were determined by Marfey’s method and by comparison of the experimental and TDDFT-calculated ECD spectra. Actinozine A possesses an unprecedented hydroperoxy moiety at C-2 of the proline moiety, while 3 and 4 possess unusual mercaptocarbamic acid and thiohydroxylamine functionalities at N-3 of the thymine moiety. The isolated compounds displayed variable cytotoxic and antimicrobial activities. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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13 pages, 2693 KiB

Open AccessArticle

Bathyptilones: Terpenoids from an Antarctic Sea Pen, Anthoptilum grandiflorum (Verrill, 1879)

by Santana A.L. Thomas, Anthony Sanchez, Younghoon Kee, Nerida G. Wilson and Bill J. Baker

Mar. Drugs 2019, 17(9), 513; https://doi.org/10.3390/md17090513 - 01 Sep 2019

Cited by 10 | Viewed by 4578

Abstract

An Antarctic coral belonging to the order Pennatulacea, collected during the 2013 austral autumn by trawl from 662 to 944 m depth, has yielded three new briarane diterpenes, bathyptilone A-C (1–3) along with a trinorditerpene, enbepeanone A (4 [...] Read more.

An Antarctic coral belonging to the order Pennatulacea, collected during the 2013 austral autumn by trawl from 662 to 944 m depth, has yielded three new briarane diterpenes, bathyptilone A-C (1–3) along with a trinorditerpene, enbepeanone A (4), which bears a new carbon skeleton. Structure elucidation was facilitated by one- and two-dimensional NMR spectroscopy, mass spectrometry and confirmed by X-ray crystallography. The three compounds were screened in four cancer cell lines. Bathyptilone A displayed selective nanomolar cytotoxicity against the neurogenic mammalian cell line Ntera-2. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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13 pages, 772 KiB

Open AccessArticle

New Peptides from The Marine-Derived Fungi Aspergillus allahabadii and Aspergillus ochraceopetaliformis

by Ji-Yeon Hwang, Jung-Ho Lee, Sung Chul Park, Jayho Lee, Dong-Chan Oh, Ki-Bong Oh and Jongheon Shin

Mar. Drugs 2019, 17(9), 488; https://doi.org/10.3390/md17090488 - 21 Aug 2019

Cited by 15 | Viewed by 3048

Abstract

Four new peptides were isolated from the culture broths of the marine-derived fungi Aspergillus allahabadii and A. ochraceopetaliformis. Based on the results of chemical and spectroscopic analyses, two compounds (1 and 2) from A. allahabadii were determined to be cyclopentapeptides, while [...] Read more.

Four new peptides were isolated from the culture broths of the marine-derived fungi Aspergillus allahabadii and A. ochraceopetaliformis. Based on the results of chemical and spectroscopic analyses, two compounds (1 and 2) from A. allahabadii were determined to be cyclopentapeptides, while those from A. ochraceopetaliformis were a structurally-related cyclodepsihexapeptide (3) and its linear analog (4). In addition to the presence of a D-amino acid residue, the almost reversed sequence of peptides in 3 and 4, relative to those of the 1 and 2, is notable. These new compounds exhibited moderate inhibition against the enzyme sortase A as well as a weak inhibition against isocitrate lyase (2). Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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13 pages, 1942 KiB

Open AccessArticle

A Collection of Bioactive Nitrogen-Containing Molecules from the Marine Sponge Acanthostrongylophora ingens

by Germana Esposito, Linh H. Mai, Arlette Longeon, Alfonso Mangoni, Emilie Durieu, Laurent Meijer, Rob Van Soest, Valeria Costantino and Marie-Lise Bourguet-Kondracki

Mar. Drugs 2019, 17(8), 472; https://doi.org/10.3390/md17080472 - 15 Aug 2019

Cited by 7 | Viewed by 3931

Abstract

Thirteen nitrogen-containing molecules (1a/1b and 2–12) were isolated from the Indonesian sponge Acanthostrongylophora ingens, highlighting the richness of this organism as a source of alkaloids. Their structures were elucidated using one- and two-dimensional NMR spectroscopy and [...] Read more.

Thirteen nitrogen-containing molecules (1a/1b and 2–12) were isolated from the Indonesian sponge Acanthostrongylophora ingens, highlighting the richness of this organism as a source of alkaloids. Their structures were elucidated using one- and two-dimensional NMR spectroscopy and HR-ESI-MS, while the stereochemistry of the diketopiperazines was established using Marfey’s method. All compounds were screened in our standard bioactivity assays, including antibacterial, antikinases, and amyloid β-42 assays. The most interesting bioactivity result was obtained with the known acanthocyclamine A (3), which revealed for the first time a specific Escherichia coli antimicrobial activity and an inhibitory effect on amyloid β-42 production induced by aftin-5 and no cytotoxicity at the dose of 26 µM. These results highlight the potentiality of a bipiperidine scaffold as a promising skeleton for preventing or reducing the production of amyloid β-42, a key player in the initiation of Alzheimer’s disease. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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12 pages, 1032 KiB

Open AccessArticle

The Purification, Characterization, and Biological Activity of New Polyketides from Mangrove-Derived Endophytic Fungus Epicoccum nigrum SCNU-F0002

by Zhangyuan Yan, Shitong Wen, Meng Ding, Huixian Guo, Cuiying Huang, Xintong Zhu, Junyi Huang, Zhigang She and Yuhua Long

Mar. Drugs 2019, 17(7), 414; https://doi.org/10.3390/md17070414 - 12 Jul 2019

Cited by 21 | Viewed by 4298

Abstract

Six new polyketides, including one coumarin (1), two isocoumarins (2 and 3), dihydroradicinin (4), and two benzofuranone derivatives (7 and 8), together with seven known analogues (5–6 and 9–13) [...] Read more.

Six new polyketides, including one coumarin (1), two isocoumarins (2 and 3), dihydroradicinin (4), and two benzofuranone derivatives (7 and 8), together with seven known analogues (5–6 and 9–13) were isolated from the culture of the mangrove endophytic fungus Epicoccum nigrum SCNU-F0002. The structures were elucidated on the interpretation of spectroscopic data. The absolute configuration of Compounds 2 and 3 were determined by comparison of their ECD spectra with the data of their analogue dihydroisocoumarins described in the literature. The absolute configuration of 4 was determined by single-crystal X-ray diffraction. All the compounds were screened for their antioxidant, antibacterial, anti-phytopathogenic fungi and cytotoxic activities. Using a DPPH radical-scavenging assay, Compounds 10–13 showed potent antioxidant activity with IC₅₀ values of 13.6, 12.1, 18.1, and 11.7 μg/mL, respectively. In addition, Compounds 6 and 7 showed antibacterial effects against Bacillus subtilis (ATCC 6538), Escherichia coli (ATCC 8739), and Staphylococcus aureus (ATCC 6538), with MIC values in the range of 25–50 μg/mL. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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