Research

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11 pages, 1939 KiB

Open AccessArticle

Ferroptosis Inhibitory Compounds from the Deep-Sea-Derived Fungus Penicillium sp. MCCC 3A00126

by You-Jia Hao, Zheng-Biao Zou, Ming-Min Xie, Yong Zhang, Lin Xu, Hao-Yu Yu, Hua-Bin Ma and Xian-Wen Yang

Mar. Drugs 2023, 21(4), 234; https://doi.org/10.3390/md21040234 - 10 Apr 2023

Cited by 6 | Viewed by 1648

Abstract

Two new xanthones (1 and 2) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds (3–36). The structures of the new compounds were established by spectroscopic data. The absolute configuration of [...] Read more.

Two new xanthones (1 and 2) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds (3–36). The structures of the new compounds were established by spectroscopic data. The absolute configuration of 1 was validated by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated for cytotoxicity and ferroptosis inhibitory activities. Compounds 14 and 15 exerted potent cytotoxicity against CCRF-CEM cells, with IC₅₀ values of 5.5 and 3.5 μM, respectively, whereas 26, 28, 33, and 34 significantly inhibited RSL3-induced ferroptosis, with EC₅₀ values of 11.6, 7.2, 11.8, and 2.2 μM, respectively. Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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15 pages, 2119 KiB

Open AccessArticle

Marine-Derived Natural Product HDYL-GQQ-495 Targets P62 to Inhibit Autophagy

by Quanfu Li, Jianjun Fan, Yinghan Chen, Yiyang Liu, Hang Liu, Wei Jiang, Dehai Li and Yongjun Dang

Mar. Drugs 2023, 21(2), 68; https://doi.org/10.3390/md21020068 - 20 Jan 2023

Cited by 1 | Viewed by 2154

Abstract

Autophagy is widely implicated in pathophysiological processes such as tumors and metabolic and neurodegenerative disorders, making it an attractive target for drug discovery. Several chemical screening approaches have been developed to uncover autophagy-modulating compounds. However, the modulation capacity of marine compounds with significant [...] Read more.

Autophagy is widely implicated in pathophysiological processes such as tumors and metabolic and neurodegenerative disorders, making it an attractive target for drug discovery. Several chemical screening approaches have been developed to uncover autophagy-modulating compounds. However, the modulation capacity of marine compounds with significant pharmacological activities is largely unknown. We constructed an EGFP^KI-LC3B cell line using the CRISPR/Cas9 knock-in strategy in which green fluorescence indicated endogenous autophagy regulation. Using this cell line, we screened a compound library of approximately 500 marine natural products and analogues to investigate molecules that altered the EGFP fluorescence. We identified eight potential candidates that enhanced EGFP fluorescence, and HDYL-GQQ-495 was the leading one. Further validation with immunoblotting demonstrated that cleaved LC3 was increased in dose- and time-dependent manners, and the autophagy adaptor P62 showed oligomerization after HDYL-GQQ-495 treatment. We also demonstrated that HDYL-GQQ-495 treatment caused autophagy substrate aggregation, which indicated that HDYL-GQQ-495 serves as an autophagy inhibitor. Furthermore, HDYL-GQQ-495 induced Gasdermin E (GSDME) cleavage and promoted pyroptosis. Moreover, HDYL-GQQ-495 directly combined with P62 to induce P62 polymerization. In P62 knockout cells, the cleavage of LC3 or GSDME was blocked after HDYL-GQQ-495 treatment. The EGFP^KI-LC3B cell line was an effective tool for autophagy modulator screening. Using this tool, we found a novel marine-derived compound, HDYL-GQQ-495, targeting P62 to inhibit autophagy and promote pyroptosis. Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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11 pages, 3588 KiB

Open AccessArticle

Chemical Constituents of the Deep-Sea-Derived Penicillium citreonigrum MCCC 3A00169 and Their Antiproliferative Effects

by Zheng-Biao Zou, Gang Zhang, Yu-Qi Zhou, Chun-Lan Xie, Ming-Min Xie, Lin Xu, You-Jia Hao, Lian-Zhong Luo, Xiao-Kun Zhang, Xian-Wen Yang and Jun-Song Wang

Mar. Drugs 2022, 20(12), 736; https://doi.org/10.3390/md20120736 - 24 Nov 2022

Cited by 2 | Viewed by 1639

Abstract

Six new citreoviridins (citreoviridins J–O, 1–6) and twenty-two known compounds (7–28) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD [...] Read more.

Six new citreoviridins (citreoviridins J–O, 1–6) and twenty-two known compounds (7–28) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J−O (1–6) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2–C-7. Pyrenocine A (7), terrein (14), and citreoviridin (20) significantly induced apoptosis for HeLa cells with IC₅₀ values of 5.4 μM, 11.3 μM, and 0.7 μM, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells. Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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11 pages, 2747 KiB

Open AccessArticle

Anti-Inflammatory Polyketide Derivatives from the Sponge-Derived Fungus Pestalotiopsis sp. SWMU-WZ04-2

by Peng Jiang, Jinfeng Luo, Yao Jiang, Liping Zhang, Liyuan Jiang, Baorui Teng, Hong Niu, Dan Zhang and Hui Lei

Mar. Drugs 2022, 20(11), 711; https://doi.org/10.3390/md20110711 - 13 Nov 2022

Cited by 2 | Viewed by 1513

Abstract

Five undescribed polyketide derivatives, pestaloketides A–E (1–5), along with eleven known analogues (6–16), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data [...] Read more.

Five undescribed polyketide derivatives, pestaloketides A–E (1–5), along with eleven known analogues (6–16), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data and electronic circular dichroism (ECD) calculations. Compounds 5, 6, 9, and 14 exhibited weak cytotoxicities against four human cancer cell lines, with IC₅₀ values ranging from 22.1 to 100 μM. Pestaloketide A (1) is an unusual polyketide, featuring a rare 5/10/5-fused ring system. Pestaloketides A (1) and B (2) exhibited moderately inhibited LPS-induced NO production activity, with IC₅₀ values of 23.6 and 14.5 μM, respectively, without cytotoxicity observed. Preliminary bioactivity evaluations and molecular docking analysis indicated that pestaloketides A (1) and B (2) had the potential to be developed into anti-inflammatory activity drug leads. Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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12 pages, 3043 KiB

Open AccessArticle

Bioactive Monoterpenes and Polyketides from the Ascidian-Derived Fungus Diaporthe sp. SYSU-MS4722

by Guifa Zhai, Senhua Chen, Hongjie Shen, Heng Guo, Minghua Jiang and Lan Liu

Mar. Drugs 2022, 20(9), 553; https://doi.org/10.3390/md20090553 - 29 Aug 2022

Cited by 3 | Viewed by 1898

Abstract

There has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered, while new monoterpenes were rarely isolated from marine-derived fungi in the past two decades. Three new monoterpenes, diaporterpenes A–C (1–3), and one [...] Read more.

There has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered, while new monoterpenes were rarely isolated from marine-derived fungi in the past two decades. Three new monoterpenes, diaporterpenes A–C (1–3), and one new α-pyrones, diaporpyrone A (6), along with nine known polyketides 4, 5, and 7–13 were isolated from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were elucidated based on extensive spectroscopic analyses (1D and 2D NMR and HR-ESIMS). The absolute configurations of 1 and 3 were identified by an X-ray crystallographic diffraction experiment using Cu-Ka radiation, and those of compound 2 were assigned by calculating NMR chemical shifts and ECD spectra. It afforded an example of natural epimers with different physical properties, especially crystallization, due to the difference in intermolecular hydrogen bonding. Compounds 9, 10, and 13 showed moderate total antioxidant capacity (0.82 of 9; 0.70 of 10; 0.48 of 13) with Trolox (total antioxidant capacity: 1.0) as a positive control, and compounds 5 and 7 showed anti-inflammatory activity with IC₅₀ values of 35.4 and 40.8 µM, respectively (positive control indomethacin: IC₅₀ = 35.8 µM). Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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10 pages, 1493 KiB

Open AccessArticle

New Carboxamides and a New Polyketide from the Sponge-Derived Fungus Arthrinium sp. SCSIO 41421

by Jianglian She, Yi Chen, Yuxiu Ye, Xiuping Lin, Bin Yang, Jiao Xiao, Yonghong Liu and Xuefeng Zhou

Mar. Drugs 2022, 20(8), 475; https://doi.org/10.3390/md20080475 - 25 Jul 2022

Cited by 7 | Viewed by 1762

Abstract

New carboxamides, (±)-vochysiamide C (1) and (+)-vochysiamide B (2), and a new polyketide, 4S,3aS,9aR-3a,9a-deoxy-3a hydroxy-1-dehydroxyarthrinone (3), were isolated and identified from the sponge-derived fungus Arthrinium sp. SCSIO 41421, together with other [...] Read more.

New carboxamides, (±)-vochysiamide C (1) and (+)-vochysiamide B (2), and a new polyketide, 4S,3aS,9aR-3a,9a-deoxy-3a hydroxy-1-dehydroxyarthrinone (3), were isolated and identified from the sponge-derived fungus Arthrinium sp. SCSIO 41421, together with other fifteen known natural products (4–18). Their structures including absolute configurations were determined by detailed NMR, MS spectroscopic analyses, calculated electronic circular dichroism (ECD), as well as quantum-chemical NMR calculations. Preliminary bioactivity screening and molecular docking analysis revealed that several natural products exhibited obvious enzyme inhibitory activities against acetylcholinesterase (AChE), such as 2,3,6,8-tetrahydroxy-1-methylxanthone (4) with an inhibitory rate 86% at 50 μg/mL. Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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12 pages, 1831 KiB

Open AccessArticle

Rare Carbon-Bridged Citrinin Dimers from the Starfish-Derived Symbiotic Fungus Penicillium sp. GGF16-1-2

by Hao Fan, Zhi-Mian Shi, Yan-Hu Lei, Mei-Xia Si-Tu, Feng-Guo Zhou, Chan Feng, Xia Wei, Xue-Hua Shao, Yang Chen and Cui-Xian Zhang

Mar. Drugs 2022, 20(7), 443; https://doi.org/10.3390/md20070443 - 06 Jul 2022

Cited by 11 | Viewed by 2059

Abstract

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G–J (1–4), and five known analogs (5–9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum [...] Read more.

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G–J (1–4), and five known analogs (5–9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1–9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD₅₀ values from 0.61 μg/mL to 16.14 μg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3). Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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10 pages, 1487 KiB

Open AccessArticle

Homo/Hetero-Dimers of Aromatic Bisabolane Sesquiterpenoids with Neuroprotective Activity from the Fungus Aspergillus versicolor A18 from South China Sea

by Han-Zhuang Weng, Jun-Yu Zhu, Fang-Yu Yuan, Zhuo-Ya Tang, Xiao-Qing Tian, Ye Chen, Cheng-Qi Fan, Gui-Hua Tang and Sheng Yin

Mar. Drugs 2022, 20(5), 322; https://doi.org/10.3390/md20050322 - 13 May 2022

Cited by 13 | Viewed by 3501

Abstract

Chromatographic fractionation of the EtOH extracts of the marine-derived fungus Aspergillus versicolor A18 has led to the isolation of 11 homo/hetero-dimers of aromatic bisabolane sesquiterpenoids including eight diphenyl ether-coupled aromatic bisabolanes (1a/1b and 5–10) and three [...] Read more.

Chromatographic fractionation of the EtOH extracts of the marine-derived fungus Aspergillus versicolor A18 has led to the isolation of 11 homo/hetero-dimers of aromatic bisabolane sesquiterpenoids including eight diphenyl ether-coupled aromatic bisabolanes (1a/1b and 5–10) and three homodimers (2–4), together with their monomers including three aromatic bisabolanes (11–13) and two diphenyl ethers (14 and 15). Their structures and absolute configurations were elucidated by extensive spectroscopic analysis including HRESIMS, 1D/2D NMR, calculated ECD, and the optical rotatory data. Among the four new compounds, (+/−)-asperbisabol A (1a/1b), asperbisabol B (2), and asperbisabol C (3), the enantiomers 1a and 1b represent an unprecedented skeleton of diphenyl ether-coupled aromatic bisabolane sesquiterpenoids with a spiroketal core moiety. The neuroprotective effects of selected compounds against sodium nitroprusside (SNP)-induced injury were evaluated in PC12 cells by the MTT assay. Five compounds (1a, 6, and 8–10) showed remarkable neuroprotective activities at 10 μM, being more active than the positive control edaravone. Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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Review

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31 pages, 3735 KiB

Open AccessReview

Secondary Metabolites from Marine-Derived Bacillus: A Comprehensive Review of Origins, Structures, and Bioactivities

by Shaoyujia Xiao, Nan Chen, Zixue Chai, Mengdie Zhou, Chenghaotian Xiao, Shiqin Zhao and Xiliang Yang

Mar. Drugs 2022, 20(9), 567; https://doi.org/10.3390/md20090567 - 06 Sep 2022

Cited by 13 | Viewed by 2501

Abstract

The marine is a highly complex ecosystem including various microorganisms. Bacillus species is a predominant microbialflora widely distributed in marine ecosystems. This review aims to provide a systematic summary of the newly reported metabolites produced by marine-derived Bacillus species over recent years covering [...] Read more.

The marine is a highly complex ecosystem including various microorganisms. Bacillus species is a predominant microbialflora widely distributed in marine ecosystems. This review aims to provide a systematic summary of the newly reported metabolites produced by marine-derived Bacillus species over recent years covering the literature from 2014 to 2021. It describes the structural diversity and biological activities of the reported compounds. Herein, a total of 87 newly reported metabolites are included in this article, among which 49 compounds originated from marine sediments, indicating that marine sediments are majority sources of productive strains of Bacillus species Therefore, marine-derived Bacillus species are a potentially promising source for the discovery of new metabolites. Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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26 pages, 10436 KiB

Open AccessReview

Deep-Sea Natural Products from Extreme Environments: Cold Seeps and Hydrothermal Vents

by Mengjing Cong, Xiaoyan Pang, Kai Zhao, Yue Song, Yonghong Liu and Junfeng Wang

Mar. Drugs 2022, 20(6), 404; https://doi.org/10.3390/md20060404 - 19 Jun 2022

Cited by 13 | Viewed by 3887

Abstract

The deep sea has been proven to be a great treasure for structurally unique and biologically active natural products in the last two decades. Cold seeps and hydrothermal vents, as typical representatives of deep-sea extreme environments, have attracted more and more attention. This [...] Read more.

The deep sea has been proven to be a great treasure for structurally unique and biologically active natural products in the last two decades. Cold seeps and hydrothermal vents, as typical representatives of deep-sea extreme environments, have attracted more and more attention. This review mainly summarizes the natural products of marine animals, marine fungi, and marine bacteria derived from deep-sea cold seeps and hydrothermal vents as well as their biological activities. In general, there were 182 compounds reported, citing 132 references and covering the literature from the first report in 1984 up to March 2022. The sources of the compounds are represented by the genera Aspergillus sp., Penicillium sp., Streptomyces sp., and so on. It is worth mentioning that 90 of the 182 compounds are new and that almost 60% of the reported structures exhibited diverse bioactivities, which became attractive targets for relevant organic synthetic and biosynthetic studies. Full article

(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)

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