Discovery of Marine Natural Products in China: Selected Papers from the 16th National Annual Conference and 2023 International Symposium on Marine Drugs (16-NASMD) Conference

A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Pharmacology".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 29421

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College of Pharmaceutical Science and Jianxing Honors College, Zhejiang University of Technology, Hangzhou, China
Interests: marine microbial natural products; antibiotics resistance; genome mining; bioinformatics; marine drugs
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China
Interests: marine drug leads; efficient discovery; biosynthesis; fermentation preparation
Special Issues, Collections and Topics in MDPI journals
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China
Interests: marine drugs; natural products; genome mining; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The biosynthetic potential of marine organisms has attracted increasing interest worldwide. The discovery of marine natural products (MNPs) with therapeutic potential has made remarkable achievements in recent years. The 16th National Annual Conference and 2023 International Symposium on Marine Drugs (16-NASMD) aim to provide a high-level international forum for scientists to present their new advances and research results regarding the discovery of MNPs. The 16-NASMD is sponsored by the Professional Committee of Marine Drugs of the Chinese Pharmaceutical Association, organized by the Institute of Marine Drugs, Zhejiang University of Technology, and held in Hangzhou, China, on 10th-12th November 2023. More detailed information about the conference can be found at https://acmp2023.sciconf.cn/cn/web/index/. This joint Special Issue will focus on bioactive natural products from the marine environment, including the following aspects:

  • The discovery, identification, and biological evaluation of new MNPs;
  • New strategies for the discovery of new and bioactive MNPs;
  • The biosynthesis, total synthesis, and structural modification of bioactive MNPs;
  • Molecular or pharmacological mechanisms of bioactive MNPs.

Please note that registration for the 16-NASMD is required for acceptance. All attendees of the conference enjoy a 20% discount on the APC to publish in this Special Issue.

Prof. Dr. Hong Wang
Prof. Dr. Huawei Zhang
Dr. Bin Wei
Guest Editors

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Published Papers (13 papers)

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Research

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15 pages, 31783 KiB  
Article
Exploring the Diversity and Specificity of Secondary Biosynthetic Potential in Rhodococcus
by Gang-Ao Hu, Yue Song, Shi-Yi Liu, Wen-Chao Yu, Yan-Lei Yu, Jian-Wei Chen, Hong Wang and Bin Wei
Mar. Drugs 2024, 22(9), 409; https://doi.org/10.3390/md22090409 - 6 Sep 2024
Viewed by 1404
Abstract
The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its [...] Read more.
The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its secondary metabolism offer valuable insights for exploring natural products, yet remain understudied. In the present study, we analyzed the distribution patterns of biosynthetic gene clusters (BGCs) in the most comprehensive Rhodococcus genome data to date. The results show that 86.5% of the gene cluster families (GCFs) are only distributed in a specific phylogenomic-clade of Rhodococcus, with the most predominant types of gene clusters being NRPS and ribosomally synthesized and post-translationally modified peptides (RiPPs). In-depth mining of RiPP gene clusters revealed that Rhodococcus encodes many clade-specific novel RiPPs, with thirteen core peptides showing antibacterial potential. High-throughput elicitor screening (HiTES) and non-targeted metabolomics revealed that a marine-derived Rhodococcus strain produces a large number of new aurachin-like compounds when exposed to specific elicitors. The present study highlights the diversity and specificity of secondary biosynthetic potential in Rhodococcus, and provides valuable information for the targeted exploration of novel natural products from Rhodococcus, especially for phylogenomic-clade-specific metabolites. Full article
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12 pages, 2774 KiB  
Article
Discovery of Prenyltransferase-Guided Hydroxyphenylacetic Acid Derivatives from Marine Fungus Penicillium sp. W21C371
by Cancan Wang, Ye Fan, Chenjie Wang, Jing Tang, Yixian Qiu, Keren Xu, Yingjia Ding, Ying Liu, Youmin Ying and Hong Wang
Mar. Drugs 2024, 22(7), 296; https://doi.org/10.3390/md22070296 - 26 Jun 2024
Viewed by 1626
Abstract
Traditional isolation methods often lead to the rediscovery of known natural products. In contrast, genome mining strategies are considered effective for the continual discovery of new natural products. In this study, we discovered a unique prenyltransferase (PT) through genome mining, capable of catalyzing [...] Read more.
Traditional isolation methods often lead to the rediscovery of known natural products. In contrast, genome mining strategies are considered effective for the continual discovery of new natural products. In this study, we discovered a unique prenyltransferase (PT) through genome mining, capable of catalyzing the transfer of a prenyl group to an aromatic nucleus to form C-C or C-O bonds. A pair of new hydroxyphenylacetic acid derivative enantiomers with prenyl units, (±)-peniprenydiol A (1), along with 16 known compounds (217), were isolated from a marine fungus, Penicillium sp. W21C371. The separation of 1 using chiral HPLC led to the isolation of the enantiomers 1a and 1b. Their structures were established on the basis of extensive spectroscopic analysis, including 1D, 2D NMR and HRESIMS. The absolute configurations of the new compounds were determined by a modified Mosher method. A plausible biosynthetic pathway for 1 was deduced, facilitated by PT catalysis. In the in vitro assay, 2 and 3 showed promising inhibitory activity against Escherichia coli β-glucuronidase (EcGUS), with IC50 values of 44.60 ± 0.84 μM and 21.60 ± 0.76 μM, respectively, compared to the positive control, D-saccharic acid 1,4-lactone hydrate (DSL). This study demonstrates the advantages of genome mining in the rational acquisition of new natural products. Full article
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11 pages, 2148 KiB  
Article
Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells
by Jie Wang, Yue-Lu Yan, Xin-Yi Yu, Jia-Yan Pan, Xin-Lian Liu, Li-Li Hong and Bin Wang
Mar. Drugs 2024, 22(4), 183; https://doi.org/10.3390/md22040183 - 19 Apr 2024
Viewed by 1799
Abstract
Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their [...] Read more.
Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 24 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 μM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial–mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT. Full article
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17 pages, 8447 KiB  
Article
Marine-Fungus-Derived Natural Compound 4-Hydroxyphenylacetic Acid Induces Autophagy to Exert Antithrombotic Effects in Zebrafish
by Shaoshuai Xin, Mengqi Zhang, Peihai Li, Lizhen Wang, Xuanming Zhang, Shanshan Zhang, Zhenqiang Mu, Houwen Lin, Xiaobin Li and Kechun Liu
Mar. Drugs 2024, 22(4), 148; https://doi.org/10.3390/md22040148 - 27 Mar 2024
Cited by 2 | Viewed by 1745
Abstract
Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Emericellopsis maritima Y39–2. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found [...] Read more.
Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Emericellopsis maritima Y39–2. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found that HPA had a strong antithrombotic activity because it can significantly increase cardiac erythrocytes, blood flow velocity, and heart rate, reduce caudal thrombus, and reverse the inflammatory response caused by Arachidonic Acid (AA). Further transcriptome analysis and qRT–PCR validation demonstrated that HPA may regulate autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to exert antithrombotic effects. Full article
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10 pages, 1692 KiB  
Article
Two New Sesquiterpenoids and a New Shikimic Acid Metabolite from Mangrove Sediment-Derived Fungus Roussoella sp. SCSIO 41427
by Zimin Xiao, Jian Cai, Ting Chen, Yilin Wang, Yixin Chen, Yongyan Zhu, Chunmei Chen, Bin Yang, Xuefeng Zhou and Huaming Tao
Mar. Drugs 2024, 22(3), 103; https://doi.org/10.3390/md22030103 - 23 Feb 2024
Cited by 2 | Viewed by 1730
Abstract
Two new sesquiterpenoid derivatives, elgonenes M (1) and N (2), and a new shikimic acid metabolite, methyl 5-O-acetyl-5-epi-shikimate (3), were isolated from the mangrove sediment-derived fungus Roussoella sp. SCSIO 41427 together with fourteen [...] Read more.
Two new sesquiterpenoid derivatives, elgonenes M (1) and N (2), and a new shikimic acid metabolite, methyl 5-O-acetyl-5-epi-shikimate (3), were isolated from the mangrove sediment-derived fungus Roussoella sp. SCSIO 41427 together with fourteen known compounds (417). The planar structures were elucidated through nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses. The relative configurations of 13 were ascertained by NOESY experiments, while their absolute configurations were determined by electronic circular dichroism (ECD) calculation. Elgonene M (1) exhibited inhibition of interleukin-1β (IL-1β) mRNA, a pro-inflammatory cytokine, at a concentration of 5 μM, with an inhibitory ratio of 31.14%. On the other hand, elgonene N (2) demonstrated inhibition at a concentration of 20 μM, with inhibitory ratios of 27.57%. Full article
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17 pages, 5670 KiB  
Article
The Peptide LLTRAGL Derived from Rapana venosa Exerts Protective Effect against Inflammatory Bowel Disease in Zebrafish Model by Regulating Multi-Pathways
by Yongna Cao, Fenghua Xu, Qing Xia, Kechun Liu, Houwen Lin, Shanshan Zhang and Yun Zhang
Mar. Drugs 2024, 22(3), 100; https://doi.org/10.3390/md22030100 - 22 Feb 2024
Cited by 2 | Viewed by 2008
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with unknown pathogenesis which has been gradually considered a public health challenge worldwide. Peptides derived from Rapana venosa have been shown to have an anti-inflammatory effect. In this study, peptide LLTRAGL derived from [...] Read more.
Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with unknown pathogenesis which has been gradually considered a public health challenge worldwide. Peptides derived from Rapana venosa have been shown to have an anti-inflammatory effect. In this study, peptide LLTRAGL derived from Rapana venosa was prepared by a solid phase synthesis technique. The protective effects of LLTRAGL were studied in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced zebrafish colitis model. The underlying mechanisms of LLTRAGL were predicted and validated by transcriptome, real-time quantitative PCR assays and molecular docking. The results showed that LLTRAGL reduced the number of macrophages migrating to the intestine, enhanced the frequency and rate of intestinal peristalsis and improved intestinal inflammatory damage. Furthermore, transcriptome analysis indicated the key pathways (NOD-like receptor signal pathway and necroptosis pathway) that link the underlying protective effects of LLTRAGL’s molecular mechanisms. In addition, the related genes in these pathways exhibited different expressions after TNBS treatment. Finally, molecular docking techniques further verified the RNA-sequencing results. In summary, LLTRAGL exerted protective effects in the model of TNBS-induced colitis zebrafish. Our findings provide valuable information for the future application of LLTRAGL in IBD. Full article
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12 pages, 1930 KiB  
Article
Development of Integrated Vectors with Strong Constitutive Promoters for High-Yield Antibiotic Production in Mangrove-Derived Streptomyces
by Mingxia Zhao, Zhiqiang Yang, Xinyue Li, Yaqi Liu, Yingying Zhang, Mengqian Zhang, Yangli Li, Xincheng Wang, Zixin Deng, Kui Hong and Dongqing Zhu
Mar. Drugs 2024, 22(2), 94; https://doi.org/10.3390/md22020094 - 18 Feb 2024
Viewed by 2320
Abstract
It is important to improve the production of bioactive secondary products for drug development. The Escherichia coli—Streptomyces shuttle vector pSET152 and its derived vector pIB139 containing a strong constitutive promoter ermEp* are commonly used as integrative vectors in actinomycetes. Four new integrative [...] Read more.
It is important to improve the production of bioactive secondary products for drug development. The Escherichia coli—Streptomyces shuttle vector pSET152 and its derived vector pIB139 containing a strong constitutive promoter ermEp* are commonly used as integrative vectors in actinomycetes. Four new integrative vectors carrying the strong constitutive promoter kasOp*, hrdBp, SCO5768p, and SP44, respectively, were constructed and proven to be functional in different mangrove-derived Streptomyces host strains by using kanamycin resistance gene neo as a reporter. Some biosynthetic genes of elaiophylins, azalomycin Fs, and armeniaspirols were selected and inserted into these vectors to overexpress in their producers including Streptomyces sp. 219807, Streptomyces sp. 211726, and S. armeniacus DSM 43125, resulting in an approximately 1.1–1.4-fold enhancement of the antibiotic yields. Full article
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16 pages, 4537 KiB  
Article
Purification and Properties of a Plasmin-like Marine Protease from Clamworm (Perinereis aibuhitensis)
by Tingting Jiang, Bing Zhang, Haixing Zhang, Mingjun Wei, Yue Su, Tuo Song, Shijia Ye, Yuping Zhu and Wenhui Wu
Mar. Drugs 2024, 22(2), 68; https://doi.org/10.3390/md22020068 - 27 Jan 2024
Viewed by 2470
Abstract
Marine organisms are a rich source of enzymes that exhibit excellent biological activity and a wide range of applications. However, there has been limited research on the proteases found in marine mudflat organisms. Based on this background, the marine fibrinolytic enzyme FELP, which [...] Read more.
Marine organisms are a rich source of enzymes that exhibit excellent biological activity and a wide range of applications. However, there has been limited research on the proteases found in marine mudflat organisms. Based on this background, the marine fibrinolytic enzyme FELP, which was isolated and purified from clamworm (Perinereis aibuhitensis), has exhibited excellent fibrinolytic activity. We demonstrated the FELP with a purification of 10.61-fold by precipitation with ammonium sulfate, ion-exchange chromatography, and gel-filtration chromatography. SDS-PAGE, fibrin plate method, and LC–MS/MS indicated that the molecular weight of FELP is 28.9 kDa and identified FELP as a fibrinolytic enzyme-like protease. FELP displayed the maximum fibrinolytic activity at pH 9 (407 ± 16 mm2) and 50 °C (724 ± 27 mm2) and had excellent stability at pH 7–11 (50%) or 30–60 °C (60%), respectively. The three-dimensional structure of some amino acid residues of FELP was predicted with the SWISS-MODEL. The fibrinolytic and fibrinogenolytic assays showed that the enzyme possessed direct fibrinolytic activity and indirect fibrinolysis via the activation of plasminogen; it could preferentially degrade Aα-chains of fibrinogen, followed by Bβ- and γ-chains. Overall, the fibrinolytic enzyme was successfully purified from Perinereis aibuhitensis, a marine Annelida (phylum), with favorable stability that has strong fibrinolysis activity in vitro. Therefore, FELP appears to be a potent fibrinolytic enzyme with an application that deserves further investigation. Full article
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11 pages, 2252 KiB  
Article
Carneusones A-F, Benzophenone Derivatives from Sponge-Derived Fungus Aspergillus carneus GXIMD00543
by Chun-Ju Lu, Li-Fen Liang, Geng-Si Zhang, Hai-Yan Li, Chun-Qing Fu, Qin Yu, Dong-Mei Zhou, Zhi-Wei Su, Kai Liu, Cheng-Hai Gao, Xin-Ya Xu and Yong-Hong Liu
Mar. Drugs 2024, 22(2), 63; https://doi.org/10.3390/md22020063 - 25 Jan 2024
Cited by 1 | Viewed by 2965
Abstract
Six benzophenone derivatives, carneusones A-F (16), along with seven known compounds (713) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum [...] Read more.
Six benzophenone derivatives, carneusones A-F (16), along with seven known compounds (713) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds 5, 6, and 8 exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC50 values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 μM, while 11 showed potent effect with an EC50 value of 2.9 ± 0.1 μM. Full article
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18 pages, 8521 KiB  
Article
New Polyene Macrolide Compounds from Mangrove-Derived Strain Streptomyces hiroshimensis GXIMD 06359: Isolation, Antifungal Activity, and Mechanism against Talaromyces marneffei
by Zhou Wang, Jianglin Yin, Meng Bai, Jie Yang, Cuiping Jiang, Xiangxi Yi, Yonghong Liu and Chenghai Gao
Mar. Drugs 2024, 22(1), 38; https://doi.org/10.3390/md22010038 - 8 Jan 2024
Viewed by 2420
Abstract
Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (14), along with seven known analogs (511), were isolated from the [...] Read more.
Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (14), along with seven known analogs (511), were isolated from the fermentation broth of the mangrove strain Streptomyces hiroshimensis GXIMD 06359. All compounds from this strain were purified using semi-preparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity-guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds exhibited broad-spectrum antifungal activity against Talaromyces marneffei with minimum inhibitory concentration (MIC) values being in the range of 2–128 μg/mL except compound 2. This is the first report of polyene derivatives produced by S. hiroshimensis as bioactive compounds against T. marneffei. In vitro studies showed that compound 1 exerted a significantly stronger antifungal activity against T. marneffei than other new compounds, and the antifungal mechanism of compound 1 may be related to the disrupted cell membrane, which causes mitochondrial dysfunction, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for compound 1 preventing and controlling talaromycosis. Full article
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12 pages, 2174 KiB  
Article
Hepialiamides A–C: Aminated Fusaric Acid Derivatives and Related Metabolites with Anti-Inflammatory Activity from the Deep-Sea-Derived Fungus Samsoniella hepiali W7
by Zheng-Biao Zou, Tai-Zong Wu, Long-He Yang, Xi-Wen He, Wen-Ya Liu, Kai Zhang, Chun-Lan Xie, Ming-Min Xie, Yong Zhang, Xian-Wen Yang and Jun-Song Wang
Mar. Drugs 2023, 21(11), 596; https://doi.org/10.3390/md21110596 - 16 Nov 2023
Cited by 2 | Viewed by 1978
Abstract
A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A–C (13) [...] Read more.
A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A–C (13) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (522). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC50 value of 426.2 nM. Full article
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Review

Jump to: Research

30 pages, 5779 KiB  
Review
Diversified Chemical Structures and Bioactivities of the Chemical Constituents Found in the Brown Algae Family Sargassaceae
by Yan Peng, Xianwen Yang, Riming Huang, Bin Ren, Bin Chen, Yonghong Liu and Hongjie Zhang
Mar. Drugs 2024, 22(2), 59; https://doi.org/10.3390/md22020059 - 24 Jan 2024
Cited by 1 | Viewed by 2202
Abstract
Sargassaceae, the most abundant family in Fucales, was recently formed through the merging of the two former families Sargassaceae and Cystoseiraceae. It is widely distributed in the world’s oceans, notably in tropical coastal regions, with the exception of the coasts of Antarctica and [...] Read more.
Sargassaceae, the most abundant family in Fucales, was recently formed through the merging of the two former families Sargassaceae and Cystoseiraceae. It is widely distributed in the world’s oceans, notably in tropical coastal regions, with the exception of the coasts of Antarctica and South America. Numerous bioactivities have been discovered through investigations of the chemical diversity of the Sargassaceae family. The secondary metabolites with unique structures found in this family have been classified as terpenoids, phlorotannins, and steroids, among others. These compounds have exhibited potent pharmacological activities. This review describes the new discovered compounds from Sargassaceae species and their associated bioactivities, citing 136 references covering from March 1975 to August 2023. Full article
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29 pages, 7518 KiB  
Review
Marine Streptomyces-Derived Novel Alkaloids Discovered in the Past Decade
by Zijun Liu, Wenyan Sun, Zhe Hu, Wei Wang and Huawei Zhang
Mar. Drugs 2024, 22(1), 51; https://doi.org/10.3390/md22010051 - 22 Jan 2024
Cited by 4 | Viewed by 3308
Abstract
Natural alkaloids originating from actinomycetes and synthetic derivatives have always been among the important suppliers of small-molecule drugs. Among their biological sources, Streptomyces is the highest and most extensively researched genus. Marine-derived Streptomyces strains harbor unconventional metabolic pathways and have been demonstrated to [...] Read more.
Natural alkaloids originating from actinomycetes and synthetic derivatives have always been among the important suppliers of small-molecule drugs. Among their biological sources, Streptomyces is the highest and most extensively researched genus. Marine-derived Streptomyces strains harbor unconventional metabolic pathways and have been demonstrated to be efficient producers of biologically active alkaloids; more than 60% of these compounds exhibit valuable activity such as antibacterial, antitumor, anti-inflammatory activities. This review comprehensively summarizes novel alkaloids produced by marine Streptomyces discovered in the past decade, focusing on their structural features, biological activity, and pharmacological mechanisms. Future perspectives on the discovery and development of novel alkaloids from marine Streptomyces are also provided. Full article
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