Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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17 pages, 3679 KiB  
Review
The Role of Natural and Synthetic Flavonoids in the Prevention of Marine Biofouling
by Daniela Pereira, Madalena Pinto, Joana R. Almeida, Marta Correia-da-Silva and Honorina Cidade
Mar. Drugs 2024, 22(2), 77; https://doi.org/10.3390/md22020077 - 2 Feb 2024
Viewed by 1611
Abstract
Marine biofouling is a major concern for the maritime industry, environment, and human health. Biocides which are currently used in marine coatings to prevent this phenomenon are toxic to the marine environment, and therefore a search for antifoulants with environmentally safe properties is [...] Read more.
Marine biofouling is a major concern for the maritime industry, environment, and human health. Biocides which are currently used in marine coatings to prevent this phenomenon are toxic to the marine environment, and therefore a search for antifoulants with environmentally safe properties is needed. A large number of scientific papers have been published showing natural and synthetic compounds with potential to prevent the attachment of macro- and microfouling marine organisms on submerged surfaces. Flavonoids are a class of compounds which are highly present in nature, including in marine organisms, and have been found in a wide range of biological activities. Some natural and synthetic flavonoids have been evaluated over the last few years for their potential to prevent the settlement and/or the growth of marine organisms on submerged structures, thereby preventing marine biofouling. This review compiles, for the first-time, natural flavonoids as well as their synthetic analogues with attributed antifouling activity against macrofouling and microfouling marine organisms. Full article
(This article belongs to the Section Marine Chemoecology for Drug Discovery)
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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
Viewed by 2408
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, 2600 KiB  
Article
Nine New Antibacterial Diterpenes and Steroids from the South China Sea Soft Coral Lobophytum catalai Tixier-Durivault
by Sheng-Hui Zhu, Yuan-Min Chang, Ming-Zhi Su, Li-Gong Yao, Song-Wei Li, Hong Wang and Yue-Wei Guo
Mar. Drugs 2024, 22(1), 50; https://doi.org/10.3390/md22010050 - 20 Jan 2024
Cited by 2 | Viewed by 1473
Abstract
Five new cembrane-type diterpenes, lobocalines A–E (15), and four new steroids, lobocaloids A–D (912), along with six known related compounds (68 and 1315) were isolated from the Yalong Bay [...] Read more.
Five new cembrane-type diterpenes, lobocalines A–E (15), and four new steroids, lobocaloids A–D (912), along with six known related compounds (68 and 1315) were isolated from the Yalong Bay soft coral Lobophytum catalai Tixier-Durivault. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ analysis, time-dependent density functional theory–electronic circular dichroism (TDDFT-ECD) calculations, X-ray diffraction analyses and comparison with the reported spectroscopic data of known compounds. Further, with the aid of X-ray diffraction analysis, the structure of lobocrasol B (15) was firmly revised as 15a. In in vitro bioassays, compound 2 showed moderate antibacterial activities against fish pathogenic bacteria Streptococcus parauberis KSP28 and Phoyobacterium damselae FP2244 with minimum inhibitory concentration (MIC) values of 8.7 and 17.3 µg/mL, respectively. All the steroids exhibited antibacterial activities against the S. parauberis KSP28 with MIC values ranging from 12.3 to 53.6 µg/mL. Compounds 2, 7 and 14 have remarkable inhibitory effects on the hemolysin production of Staphylococcus aureus, while compounds 812 have medium inhibitory effects on the pyocyanin production in Pseudomonas aeruginosa. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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16 pages, 3103 KiB  
Article
αO-Conotoxin GeXIVA[1,2] Reduced Neuropathic Pain and Changed Gene Expression in Chronic Oxaliplatin-Induced Neuropathy Mice Model
by Huanbai Wang, Xiaodan Li, Yamin Qiao, Meiting Wang, Wen Wang, J. Michael McIntosh, Dongting Zhangsun and Sulan Luo
Mar. Drugs 2024, 22(1), 49; https://doi.org/10.3390/md22010049 - 19 Jan 2024
Cited by 2 | Viewed by 1841
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the α9α10 nicotinic acetylcholine receptor (nAChR)-specific antagonist αO-conotoxin GeXIVA[1,2] is effective in CIPN models; however, the [...] Read more.
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the α9α10 nicotinic acetylcholine receptor (nAChR)-specific antagonist αO-conotoxin GeXIVA[1,2] is effective in CIPN models; however, the related mechanisms remain unclear. Here, we analyzed the preventive effect of GeXIVA[1,2] on neuropathic pain in the long-term oxaliplatin injection-induced CIPN model. At the end of treatment, lumbar (L4-L6) spinal cord was extracted, and RNA sequencing and bioinformatic analysis were performed to investigate the potential genes and pathways related to CIPN and GeXIVA[1,2]. GeXIVA[1,2] inhibited the development of mechanical allodynia induced by chronic oxaliplatin treatment. Repeated injections of GeXIVA[1,2] for 3 weeks had no effect on the mice’s normal pain threshold or locomotor activity and anxiety-like behavior, as evaluated in the open field test (OFT) and elevated plus maze (EPM). Our RNA sequencing results identified 209 differentially expressed genes (DEGs) in the CIPN model, and simultaneously injecting GeXIVA[1,2] with oxaliplatin altered 53 of the identified DEGs. These reverted genes were significantly enriched in immune-related pathways represented by the cytokine–cytokine receptor interaction pathway. Our findings suggest that GeXIVA[1,2] could be a potential therapeutic compound for chronic oxaliplatin-induced CIPN management. Full article
(This article belongs to the Special Issue Conotoxin and Conotoxin Analogues: A Pharmacy Cabinet under the Sea)
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21 pages, 1451 KiB  
Review
Alexandrium spp.: From Toxicity to Potential Biotechnological Benefits
by Eleonora Montuori, Daniele De Luca, Antonella Penna, Darta Stalberga and Chiara Lauritano
Mar. Drugs 2024, 22(1), 31; https://doi.org/10.3390/md22010031 - 30 Dec 2023
Viewed by 2174
Abstract
Many dinoflagellates of the genus Alexandrium are well known for being responsible for harmful algal blooms (HABs), producing potent toxins that cause damages to other marine organisms, aquaculture, fishery, tourism, as well as induce human intoxications and even death after consumption of contaminated [...] Read more.
Many dinoflagellates of the genus Alexandrium are well known for being responsible for harmful algal blooms (HABs), producing potent toxins that cause damages to other marine organisms, aquaculture, fishery, tourism, as well as induce human intoxications and even death after consumption of contaminated shellfish or fish. In this review, we summarize potential bioprospecting associated to the genus Alexandrium, including which Alexandrium spp. produce metabolites with anticancer, antimicrobial, antiviral, as well as anti-Alzheimer applications. When available, we report their mechanisms of action and targets. We also discuss recent progress on the identification of secondary metabolites with biological properties favorable to human health and aquaculture. Altogether, this information highlights the importance of studying which culturing conditions induce the activation of enzymatic pathways responsible for the synthesis of bioactive metabolites. It also suggests considering and comparing clones collected in different locations for toxin monitoring and marine bioprospecting. This review can be of interest not only for the scientific community, but also for the entire population and industries. Full article
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17 pages, 2589 KiB  
Article
Chlorinated Enyne Fatty Acid Amides from a Marine Cyanobacterium: Discovery of Taveuniamides L-M and Pharmacological Characterization of Taveuniamide F as a GPCR Antagonist with CNR1 Selectivity
by Lobna A. Elsadek, Emma K. Ellis, Gustavo Seabra, Valerie J. Paul and Hendrik Luesch
Mar. Drugs 2024, 22(1), 28; https://doi.org/10.3390/md22010028 - 30 Dec 2023
Viewed by 3053
Abstract
NMR and MS/MS-based metabolomics of a cyanobacterial extract from Piti Bomb Holes, Guam, indicated the presence of unique enyne-containing halogenated fatty acid amides. We isolated three new compounds of this class, taveuniamides L-N (13), along with the previously [...] Read more.
NMR and MS/MS-based metabolomics of a cyanobacterial extract from Piti Bomb Holes, Guam, indicated the presence of unique enyne-containing halogenated fatty acid amides. We isolated three new compounds of this class, taveuniamides L-N (13), along with the previously reported taveuniamide F (4), which was the most abundant analog. The planar structures of the new compounds were established using 1D and 2D NMR as well as mass spectrometry. We established the configuration of this chemical class to be R at C-8 via Mosher’s analysis of 4 after reduction of the carboxamide group. Our biological investigations with 4 revealed that the compound binds to the cannabinoid receptor CNR1, acting as an antagonist/inverse agonist in the canonical G-protein signaling pathways. In selectivity profiling against 168 GPCR targets using the β-arrestin functional assay, we found that 4 antagonizes GPR119, NPSR1b, CCR9, CHRM4, GPR120, HTR2A, and GPR103, in addition to CNR1. Interestingly, 4 showed a 6.8-fold selectivity for CNR1 over CNR2. The binding mode of 4 to CNR1 was investigated using docking and molecular dynamics simulations with both natural and unnatural stereoisomers, revealing important CNR1 residues for the interaction and also providing a possible reasoning for the observed CNR1/CNR2 selectivity. Full article
(This article belongs to the Special Issue Bioactive Product from Marine Cyanobacteria)
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14 pages, 2208 KiB  
Article
Indole Diketopiperazine Alkaloids from the Marine Sediment-Derived Fungus Aspergillus chevalieri against Pancreatic Ductal Adenocarcinoma
by Dina H. El-Kashef, Deborah D. Obidake, Katja Schiedlauske, Alina Deipenbrock, Sebastian Scharf, Hao Wang, Daniela Naumann, Daniel Friedrich, Simone Miljanovic, Takin Haj Hassani Sohi, Christoph Janiak, Klaus Pfeffer and Nicole Teusch
Mar. Drugs 2024, 22(1), 5; https://doi.org/10.3390/md22010005 - 20 Dec 2023
Viewed by 1748
Abstract
A new prenylated indole diketopiperazine alkaloid, rubrumline P (1), was isolated along with six more analogues and characterized from the fermentation culture of a marine sediment-derived fungus, Aspergillus chevalieri, collected at a depth of 15 m near the lighthouse in [...] Read more.
A new prenylated indole diketopiperazine alkaloid, rubrumline P (1), was isolated along with six more analogues and characterized from the fermentation culture of a marine sediment-derived fungus, Aspergillus chevalieri, collected at a depth of 15 m near the lighthouse in Dahab, Red Sea, Egypt. In the current study, a bioassay-guided fractionation allowed for the identification of an active fraction displaying significant cytotoxic activity against the human pancreatic adenocarcinoma cell line PANC-1 from the EtOAc extract of the investigated fungus compared to the standard paclitaxel. The structures of the isolated compounds from the active fraction were established using 1D/2D NMR spectroscopy and mass spectrometry, together with comparisons with the literature. The absolute configuration of the obtained indole diketopiperazines was established based on single-crystal X-ray diffraction analyses of rubrumline I (2) and comparisons of optical rotations and NMR data, as well as on biogenetic considerations. Genome sequencing indicated the formation of prenyltransferases, which was subsequently confirmed by the isolation of mono-, di-, tri-, and tetraprenylated compounds. Compounds rubrumline P (1) and neoechinulin D (4) confirmed preferential cytotoxic activity against PANC-1 cancer cells with IC50 values of 25.8 and 23.4 µM, respectively. Although the underlying mechanism-of-action remains elusive in this study, cell cycle analysis indicated a slight increase in the sub-G1 peak after treatment with compounds 1 and 4. Full article
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15 pages, 4213 KiB  
Article
Karenia brevis Extract Induces Cellular Entry through Distinct Mechanisms in Phagocytic RAW 264.7 Macrophages versus Non-Phagocytic Vero Cells
by Laurie A. Minns, Kathryn T. Sausman, Ariel P. Brown, Robert A. York and Jennifer R. McCall
Mar. Drugs 2024, 22(1), 4; https://doi.org/10.3390/md22010004 - 19 Dec 2023
Viewed by 1438
Abstract
Marine algae extracts are an important area of potential drug discovery; however, nearly all studies to date have used non-fluorescent-based methods to determine changes in target cell activity. Many of the most robust immunological and cellular analyses rely on fluorescent probes and readouts, [...] Read more.
Marine algae extracts are an important area of potential drug discovery; however, nearly all studies to date have used non-fluorescent-based methods to determine changes in target cell activity. Many of the most robust immunological and cellular analyses rely on fluorescent probes and readouts, which can be problematic when the algae extract is fluorescent itself. In this study, we identified the fluorescent spectrum of an isolated extract from the marine dinoflagellate Karenia brevis, which included two fluorescing components: chlorophyll α and pheophytin α. When excited at 405 nm and 664 nm, the extract emitted fluorescence at 676 nm and 696 nm, respectively. The extract and its fluorescing components, chlorophyll α and pheophytin α, entered phagocytic RAW 264.7 macrophages and non-phagocytic Vero kidney cells through distinct mechanisms. When incubated with the extract and its main components, both the RAW 264.7 macrophages and the Vero cells accumulated fluorescence as early as 30 min and continued through 48 h. Vero kidney cells accumulated the K. brevis fluorescent extract through a dynamin-independent and acidified endosomal-dependent mechanism. RAW 264.7 macrophages accumulated fluorescent extract through a dynamin-independent, acidified endosomal-independent mechanism, which supports accumulation through phagocytosis. Furthermore, RAW 264.7 macrophages downregulated cell-surface expression of CD206 in response to extract stimulation indicating activation of phagocytic responses and potential immunosuppression of these immune cells. This study represents the first characterization of the cellular update of K. brevis extracts in phagocytic versus non-phagocytic cells. The data suggest the importance of understanding cellular uptake of fluorescing algae extracts and their mechanism of action for future drug discovery efforts. Full article
(This article belongs to the Section Marine Pharmacology)
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15 pages, 5294 KiB  
Article
Rapid Discovery of Substances with Anticancer Potential from Marine Fungi Based on a One Strain–Many Compounds Strategy and UPLC-QTOF-MS
by Yu-Ting Wu, Xiao-Na Zhao, Pei-Xi Zhang, Cui-Fang Wang, Jing Li, Xiao-Yue Wei, Jia-Qi Shi, Wang Dai, Qi Zhang and Jie-Qing Liu
Mar. Drugs 2023, 21(12), 646; https://doi.org/10.3390/md21120646 - 18 Dec 2023
Cited by 1 | Viewed by 1806
Abstract
The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A [...] Read more.
The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth. Full article
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15 pages, 2539 KiB  
Article
New Eremophilane-Type Sesquiterpenes from the Marine Sediment-Derived Fungus Emericellopsis maritima BC17 and Their Cytotoxic and Antimicrobial Activities
by Jorge R. Virués-Segovia, Carlos Millán, Cristina Pinedo, Victoria E. González-Rodríguez, Sokratis Papaspyrou, David Zorrilla, Thomas A. Mackenzie, María C. Ramos, Mercedes de la Cruz, Josefina Aleu and Rosa Durán-Patrón
Mar. Drugs 2023, 21(12), 634; https://doi.org/10.3390/md21120634 - 11 Dec 2023
Cited by 2 | Viewed by 2489
Abstract
The fungal strain BC17 was isolated from sediments collected in the intertidal zone of the inner Bay of Cadiz and characterized as Emericellopsis maritima. On the basis of the one strain–many compounds (OSMAC) approach, four new eremophilane-type sesquiterpenes (14 [...] Read more.
The fungal strain BC17 was isolated from sediments collected in the intertidal zone of the inner Bay of Cadiz and characterized as Emericellopsis maritima. On the basis of the one strain–many compounds (OSMAC) approach, four new eremophilane-type sesquiterpenes (14), together with thirteen known derivatives (517) and two reported diketopiperazines (18, 19), were isolated from this strain. The chemical structures and absolute configurations of the new compounds were determined through extensive NMR and HRESIMS spectroscopic studies and ECD calculation. Thirteen of the isolated eremophilanes were examined for cytotoxic and antimicrobial activities. PR toxin (16) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058, and Mia PaCa-2 human cancer cell lines with IC50 values ranging from 3.75 to 33.44 µM. (+)-Aristolochene (10) exhibited selective activity against the fungal strains Aspergillus fumigatus ATCC46645 and Candida albicans ATCC64124 at 471 µM. Full article
(This article belongs to the Special Issue Marine Drugs Research in Spain 2nd Edition)
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20 pages, 5632 KiB  
Review
Biotechnological Potential of Macroalgae during Seasonal Blooms for Sustainable Production of UV-Absorbing Compounds
by Nedeljka Rosic and Carol Thornber
Mar. Drugs 2023, 21(12), 633; https://doi.org/10.3390/md21120633 - 8 Dec 2023
Viewed by 2100
Abstract
Marine macroalgae (seaweeds) are important primary global producers, with a wide distribution in oceans around the world from polar to tropical regions. Most of these species are exposed to variable environmental conditions, such as abiotic (e.g., light irradiance, temperature variations, nutrient availability, salinity [...] Read more.
Marine macroalgae (seaweeds) are important primary global producers, with a wide distribution in oceans around the world from polar to tropical regions. Most of these species are exposed to variable environmental conditions, such as abiotic (e.g., light irradiance, temperature variations, nutrient availability, salinity levels) and biotic factors (e.g., grazing and pathogen exposure). As a result, macroalgae developed numerous important strategies to increase their adaptability, including synthesizing secondary metabolites, which have promising biotechnological applications, such as UV-absorbing Mycosporine-Like Amino Acid (MAAs). MAAs are small, water-soluble, UV-absorbing compounds that are commonly found in many marine organisms and are characterized by promising antioxidative, anti-inflammatory and photoprotective properties. However, the widespread use of MAAs by humans is often restricted by their limited bioavailability, limited success in heterologous expression systems, and low quantities recovered from the natural environment. In contrast, bloom-forming macroalgal species from all three major macroalgal clades (Chlorophyta, Phaeophyceae, and Rhodophyta) occasionally form algal blooms, resulting in a rapid increase in algal abundance and high biomass production. This review focuses on the bloom-forming species capable of producing pharmacologically important compounds, including MAAs, and the application of proteomics in facilitating macroalgal use in overcoming current environmental and biotechnological challenges. Full article
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27 pages, 4278 KiB  
Review
Therapeutic Potential of Marine-Derived Cyclic Peptides as Antiparasitic Agents
by Ricardo Ribeiro, Lia Costa, Eugénia Pinto, Emília Sousa and Carla Fernandes
Mar. Drugs 2023, 21(12), 609; https://doi.org/10.3390/md21120609 - 25 Nov 2023
Cited by 3 | Viewed by 3982
Abstract
Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. [...] Read more.
Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. Marine-derived cyclic peptides have been increasingly screened as candidates for developing new drugs. Therefore, in this review, a systematic analysis of the scientific literature was performed and 25 marine-derived cyclic peptides with antiparasitic activity (125) were found. Antimalarial activity is the most reported (51%), followed by antileishmanial (27%) and antitrypanosomal (20%) activities. Some compounds showed promising antiparasitic activity at the nM scale, being active against various parasites. The mechanisms of action and targets for some of the compounds have been investigated, revealing different strategies against parasites. Full article
(This article belongs to the Special Issue Marine Antiparasitic Agents)
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14 pages, 1412 KiB  
Article
Lecanicilliums A–F, Thiodiketopiperazine-Class Alkaloids from a Mangrove Sediment-Derived Fungus Lecanicillium kalimantanense
by Lin-Fang Zhong, Juan Ling, Lian-Xiang Luo, Chang-Nian Yang, Xiao Liang and Shu-Hua Qi
Mar. Drugs 2023, 21(11), 575; https://doi.org/10.3390/md21110575 - 31 Oct 2023
Cited by 1 | Viewed by 1594
Abstract
Six new thiodiketopiperazine-class alkaloids lecanicilliums A–F were isolated from the mangrove sediment-derived fungus Lecanicillium kalimantanense SCSIO41702, together with thirteen known analogues. Their structures were determined by spectroscopic analysis. The absolute configurations were determined by quantum chemical calculations. Electronic circular dichroism (ECD) spectra and [...] Read more.
Six new thiodiketopiperazine-class alkaloids lecanicilliums A–F were isolated from the mangrove sediment-derived fungus Lecanicillium kalimantanense SCSIO41702, together with thirteen known analogues. Their structures were determined by spectroscopic analysis. The absolute configurations were determined by quantum chemical calculations. Electronic circular dichroism (ECD) spectra and the structure of Lecanicillium C were further confirmed by a single-crystal X-ray diffraction analysis. Lecanicillium A contained an unprecedented 6/5/6/5/7/6 cyclic system with a spirocyclic center at C-2′. Biologically, lecanicillium E, emethacin B, and versicolor A displayed significant cytotoxicity against human lung adenocarcinoma cell line H1975, with IC50 values of 7.2~16.9 μM, and lecanicillium E also showed antibacterial activity against four pathogens with MIC values of 10~40 μg/mL. Their structure–activity relationship is also discussed. Full article
(This article belongs to the Special Issue Natural Products Isolated from Marine Sediment)
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12 pages, 1083 KiB  
Article
Chemical Constituents from Soft Coral Clavularia spp. Demonstrate Antiproliferative Effects on Oral Cancer Cells
by Ming-Ya Cheng, Ya-Ting Chuang, Hsueh-Wei Chang, Zheng-Yu Lin, Ching-Yeu Chen and Yuan-Bin Cheng
Mar. Drugs 2023, 21(10), 529; https://doi.org/10.3390/md21100529 - 8 Oct 2023
Cited by 1 | Viewed by 1392
Abstract
Five new eudensamane-type sesquiterpene lactones, clasamanes A–E (15), three new dolabellane-type diterpenes, clabellanes A–C (68), and fifteen known compounds (923) were isolated from the ethanolic extract of Taiwanese soft coral Clavularia [...] Read more.
Five new eudensamane-type sesquiterpene lactones, clasamanes A–E (15), three new dolabellane-type diterpenes, clabellanes A–C (68), and fifteen known compounds (923) were isolated from the ethanolic extract of Taiwanese soft coral Clavularia spp. The structures of all undescribed components (18) were determined by analysis of IR, mass, NMR, and UV spectroscopic data. The absolute configuration of new compounds was determined by using circular dichroism and DP4+ calculations. The cytotoxic activities of all isolated marine natural products were evaluated. Compound 7 showed a significant cytotoxic effect against oral cancer cell line (Ca9-22) with an IC50 value of 7.26 ± 0.17 μg/mL. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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19 pages, 5983 KiB  
Article
Structural Diversity and Biological Activity of Cyanopeptolins Produced by Nostoc edaphicum CCNP1411
by Robert Konkel, Marta Cegłowska, Karolina Szubert, Ewa Wieczerzak, Sofia Iliakopoulou, Triantafyllos Kaloudis and Hanna Mazur-Marzec
Mar. Drugs 2023, 21(10), 508; https://doi.org/10.3390/md21100508 - 26 Sep 2023
Cited by 2 | Viewed by 3443
Abstract
Cyanopeptolins (CPs) are one of the most commonly occurring class of cyanobacterial nonribosomal peptides. For the majority of these compounds, protease inhibition has been reported. In the current work, the structural diversity of cyanopeptolins produced by Nostoc edaphicum CCNP1411 was explored. As a [...] Read more.
Cyanopeptolins (CPs) are one of the most commonly occurring class of cyanobacterial nonribosomal peptides. For the majority of these compounds, protease inhibition has been reported. In the current work, the structural diversity of cyanopeptolins produced by Nostoc edaphicum CCNP1411 was explored. As a result, 93 CPs, including 79 new variants, were detected and structurally characterized based on their mass fragmentation spectra. CPs isolated in higher amounts were additionally characterized by NMR. To the best of our knowledge, this is the highest number of cyanopeptides found in one strain. The biological assays performed with the 34 isolated CPs confirmed the significance of the amino acid located between Thr and the unique 3-amino-6-hydroxy-2-piperidone (Ahp) on the activity of the compounds against serine protease and HeLa cancer cells. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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20 pages, 3636 KiB  
Article
A Chemo-Ecological Investigation of Dendrilla antarctica Topsent, 1905: Identification of Deceptionin and the Effects of Heat Stress and Predation Pressure on Its Terpene Profiles
by Paula De Castro-Fernández, Carlos Angulo-Preckler, Cristina García-Aljaro, Conxita Avila and Adele Cutignano
Mar. Drugs 2023, 21(9), 499; https://doi.org/10.3390/md21090499 - 19 Sep 2023
Cited by 1 | Viewed by 1105
Abstract
Marine sponges usually host a wide array of secondary metabolites that play crucial roles in their biological interactions. The factors that influence the intraspecific variability in the metabolic profile of organisms, their production or ecological function remain generally unknown. Understanding this may help [...] Read more.
Marine sponges usually host a wide array of secondary metabolites that play crucial roles in their biological interactions. The factors that influence the intraspecific variability in the metabolic profile of organisms, their production or ecological function remain generally unknown. Understanding this may help predict changes in biological relationships due to environmental variations as a consequence of climate change. The sponge Dendrilla antarctica is common in shallow rocky bottoms of the Antarctic Peninsula and is known to produce diterpenes that are supposed to have defensive roles. Here we used GC-MS to determine the major diterpenes in two populations of D. antarctica from two islands, Livingston and Deception Island (South Shetland Islands). To assess the potential effect of heat stress, we exposed the sponge in aquaria to a control temperature (similar to local), heat stress (five degrees higher) and extreme heat stress (ten degrees higher). To test for defence induction by predation pressure, we exposed the sponges to the sea star Odontaster validus and the amphipod Cheirimedon femoratus. Seven major diterpenes were isolated and identified from the samples. While six of them were already reported in the literature, we identified one new aplysulphurane derivative that was more abundant in the samples from Deception Island, so we named it deceptionin (7). The samples were separated in the PCA space according to the island of collection, with 9,11-dihydrogracilin A (1) being more abundant in the samples from Livingston, and deceptionin (7) in the samples from Deception. We found a slight effect of heat stress on the diterpene profiles of D. antarctica, with tetrahydroaplysulphurin-1 (6) and the gracilane norditerpene 2 being more abundant in the group exposed to heat stress. Predation pressure did not seem to influence the metabolite production. Further research on the bioactivity of D. antarctica secondary metabolites, and their responses to environmental changes will help better understand the functioning and fate of the Antarctic benthos. Full article
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17 pages, 5543 KiB  
Article
Talarolides Revisited: Cyclic Heptapeptides from an Australian Marine Tunicate-Associated Fungus, Talaromyces sp. CMB-TU011
by Angela A. Salim, Waleed M. Hussein, Pradeep Dewapriya, Huy N. Hoang, Yahao Zhou, Kaumadi Samarasekera, Zeinab G. Khalil, David P. Fairlie and Robert J. Capon
Mar. Drugs 2023, 21(9), 487; https://doi.org/10.3390/md21090487 - 11 Sep 2023
Cited by 1 | Viewed by 2778
Abstract
Application of a miniaturized 24-well plate system for cultivation profiling (MATRIX) permitted optimization of the cultivation conditions for the marine-derived fungus Talaromyces sp. CMB-TU011, facilitating access to the rare cycloheptapeptide talarolide A (1) along with three new analogues, B–D (2 [...] Read more.
Application of a miniaturized 24-well plate system for cultivation profiling (MATRIX) permitted optimization of the cultivation conditions for the marine-derived fungus Talaromyces sp. CMB-TU011, facilitating access to the rare cycloheptapeptide talarolide A (1) along with three new analogues, B–D (24). Detailed spectroscopic analysis supported by Marfey’s analysis methodology was refined to resolve N-Me-l-Ala from N-Me-d-Ala, l-allo-Ile from l-Ile and l-Leu, and partial and total syntheses of 2, and permitted unambiguous assignment of structures for 1 (revised) and 24. Consideration of diagnostic ROESY correlations for the hydroxamates 1 and 34, and a calculated solution structure for 1, revealed how cross-ring H-bonding to the hydroxamate moiety influences (defines/stabilizes) the cyclic peptide conformation. Such knowledge draws attention to the prospect that hydroxamates may be used as molecular bridges to access new cyclic peptide conformations, offering the prospect of new biological properties, including enhanced oral bioavailability. Full article
(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products)
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20 pages, 7103 KiB  
Article
Spatial Distribution and Biochemical Characterization of Serine Peptidase Inhibitors in the Venom of the Brazilian Sea Anemone Anthopleura cascaia Using Mass Spectrometry Imaging
by Daiane Laise da Silva, Rodrigo Valladão, Emidio Beraldo-Neto, Guilherme Rabelo Coelho, Oscar Bento da Silva Neto, Hugo Vigerelli, Adriana Rios Lopes, Brett R. Hamilton, Eivind A. B. Undheim, Juliana Mozer Sciani and Daniel Carvalho Pimenta
Mar. Drugs 2023, 21(9), 481; https://doi.org/10.3390/md21090481 - 30 Aug 2023
Viewed by 1456
Abstract
Sea anemones are known to produce a diverse array of toxins with different cysteine-rich peptide scaffolds in their venoms. The serine peptidase inhibitors, specifically Kunitz inhibitors, are an important toxin family that is believed to function as defensive peptides, as well as prevent [...] Read more.
Sea anemones are known to produce a diverse array of toxins with different cysteine-rich peptide scaffolds in their venoms. The serine peptidase inhibitors, specifically Kunitz inhibitors, are an important toxin family that is believed to function as defensive peptides, as well as prevent proteolysis of other secreted anemone toxins. In this study, we isolated three serine peptidase inhibitors named Anthopleura cascaia peptide inhibitors I, II, and III (ACPI-I, ACPI-II, and ACPI-III) from the venom of the endemic Brazilian sea anemone A. cascaia. The venom was fractionated using RP-HPLC, and the inhibitory activity of these fractions against trypsin was determined and found to range from 59% to 93%. The spatial distribution of the anemone peptides throughout A. cascaia was observed using mass spectrometry imaging. The inhibitory peptides were found to be present in the tentacles, pedal disc, and mesenterial filaments. We suggest that the three inhibitors observed during this study belong to the venom Kunitz toxin family on the basis of their similarity to PI-actitoxin-aeq3a-like and the identification of amino acid residues that correspond to a serine peptidase binding site. Our findings expand our understanding of the diversity of toxins present in sea anemone venom and shed light on their potential role in protecting other venom components from proteolysis. Full article
(This article belongs to the Section Marine Toxins)
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20 pages, 2442 KiB  
Article
An Investigation of Structure–Activity Relationships and Cell Death Mechanisms of the Marine Alkaloids Discorhabdins in Merkel Cell Carcinoma Cells
by Maria Orfanoudaki, Emily A. Smith, Natasha T. Hill, Khalid A. Garman, Isaac Brownell, Brent R. Copp, Tanja Grkovic and Curtis J. Henrich
Mar. Drugs 2023, 21(9), 474; https://doi.org/10.3390/md21090474 - 29 Aug 2023
Cited by 2 | Viewed by 2957
Abstract
A library of naturally occurring and semi-synthetic discorhabdins was assessed for their effects on Merkel cell carcinoma (MCC) cell viability. The set included five new natural products and semi-synthetic compounds whose structures were elucidated with NMR, HRMS, and ECD techniques. Several discorhabdins averaged [...] Read more.
A library of naturally occurring and semi-synthetic discorhabdins was assessed for their effects on Merkel cell carcinoma (MCC) cell viability. The set included five new natural products and semi-synthetic compounds whose structures were elucidated with NMR, HRMS, and ECD techniques. Several discorhabdins averaged sub-micromolar potency against the MCC cell lines tested and most of the active compounds showed selectivity towards virus-positive MCC cell lines. An investigation of structure–activity relationships resulted in an expanded understanding of the crucial structural features of the discorhabdin scaffold. Mechanistic cell death assays suggested that discorhabdins, unlike many other MCC-active small molecules, do not induce apoptosis, as shown by the lack of caspase activation, annexin V staining, and response to caspase inhibition. Similarly, discorhabdin treatment failed to increase MCC intracellular calcium and ROS levels. In contrast, the rapid loss of cellular reducing potential and mitochondrial membrane potential suggested that discorhabdins induce mitochondrial dysfunction leading to non-apoptotic cell death. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 3.0)
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13 pages, 2613 KiB  
Article
Butanolides and Butenolides from a Marine-Derived Streptomyces sp. Exert Neuroprotective Activity through Activation of the TrkB Neurotrophin Receptor
by Paolo Giaccio, Despoina Charou, Dafni-Ioanna Diakaki, Anna Chita, Achille Gravanis, Ioannis Charalampopoulos, Vassilios Roussis and Efstathia Ioannou
Mar. Drugs 2023, 21(9), 465; https://doi.org/10.3390/md21090465 - 25 Aug 2023
Viewed by 2467
Abstract
Neurodegenerative diseases are incurable and debilitating conditions, characterized by progressive loss and degeneration of vulnerable neuronal populations. Currently, there are no effective therapies available for the treatment of most neurodegenerative disorders. A panel of extracts exhibiting interesting chemical profiles among a high number [...] Read more.
Neurodegenerative diseases are incurable and debilitating conditions, characterized by progressive loss and degeneration of vulnerable neuronal populations. Currently, there are no effective therapies available for the treatment of most neurodegenerative disorders. A panel of extracts exhibiting interesting chemical profiles among a high number of bacterial strains isolated from East Mediterranean marine sediments and macroorganisms were evaluated for their activity on TrkB-expressing cells. Among them, the actinobacterial strain Streptomyces sp. BI0788, exhibiting neuroprotective activity in vitro, was selected and cultivated in large-scale. The chemical analysis of its organic extract resulted in the isolation of four new butanolides (1, 46), along with two previously reported butanolides (2 and 3) and eight previously reported butenolides (714). Compounds 24 and 714 were evaluated for their neuroprotective effects on TrkB-expressing NIH-3T3 cells. Among them, metabolites 3, 4, 7, 10, 11, 13 and 14 exhibited significant protective activity on the aforementioned cells through the activation of TrkB, the high-affinity receptor for the Brain-Derived Neurotrophic Factor (BDNF), which is well known to play a crucial role in neuronal cell survival and maintenance. Full article
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14 pages, 2935 KiB  
Article
Lobosteroids A–F: Six New Highly Oxidized Steroids from the Chinese Soft Coral Lobophytum sp.
by Zi-Yi Xia, Man-Man Sun, Yang Jin, Li-Gong Yao, Ming-Zhi Su, Lin-Fu Liang, Hong Wang and Yue-Wei Guo
Mar. Drugs 2023, 21(8), 457; https://doi.org/10.3390/md21080457 - 19 Aug 2023
Cited by 1 | Viewed by 2788
Abstract
To explore the steroidal constituents of the soft coral Lobophytum sp. at the coast of Xuwen County, Guangdong Province, China, a chemical investigation of the above-mentioned soft coral was carried out. After repeated column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC, [...] Read more.
To explore the steroidal constituents of the soft coral Lobophytum sp. at the coast of Xuwen County, Guangdong Province, China, a chemical investigation of the above-mentioned soft coral was carried out. After repeated column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC, six new steroids, namely lobosteroids A–F (16), along with four known compounds 710, were obtained. Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data reported in the literature. Among them, the absolute configuration of 1 was determined by X-ray diffraction analysis using Cu Kα radiation. These steroids were characterized by either the presence of an α,β-α′,β′-unsaturated carbonyl, or an α,β-unsaturated carbonyl moiety in ring A, or the existence of a 5α,8α-epidioxy system in ring B, as well as diverse oxidation of side chains. The antibacterial bioassays showed that all isolated steroids exhibited significant inhibitory activities against the fish pathogenic bacteria Streptococcus parauberis FP KSP28, Phoyobacterium damselae FP2244, and Streptococcus parauberis SPOF3K, with IC90 values ranging from 0.1 to 11.0 µM. Meanwhile, compounds 2 and 610 displayed potent inhibitory effects against the vancomycin-resistant Enterococcus faecium bacterium G7 with IC90 values ranging from 4.4 to 18.3 µM. Therefore, ten highly oxidized steroids with strong antibacterial activities were isolated from the Chinese soft coral Lobophytum sp., which could be developed as new chemotypes of antibacterial drug leads. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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13 pages, 1588 KiB  
Article
MariClus: Your One-Stop Platform for Information on Marine Natural Products, Their Gene Clusters and Producing Organisms
by Cedric Hermans, Maarten Lieven De Mol, Marieke Mispelaere, Anne-Sofie De Rop, Jeltien Rombaut, Tesneem Nusayr, Rebecca Creamer, Sofie L. De Maeseneire, Wim K. Soetaert and Paco Hulpiau
Mar. Drugs 2023, 21(8), 449; https://doi.org/10.3390/md21080449 - 15 Aug 2023
Viewed by 3191
Abstract
Background: The marine environment hosts the vast majority of living species and marine microbes that produce natural products with great potential in providing lead compounds for drug development. With over 70% of Earth’s surface covered in water and the high interaction rate associated [...] Read more.
Background: The marine environment hosts the vast majority of living species and marine microbes that produce natural products with great potential in providing lead compounds for drug development. With over 70% of Earth’s surface covered in water and the high interaction rate associated with liquid environments, this has resulted in many marine natural product discoveries. Our improved understanding of the biosynthesis of these molecules, encoded by gene clusters, along with increased genomic information will aid us in uncovering even more novel compounds. Results: We introduce MariClus (https://www.mariclus.com), an online user-friendly platform for mining and visualizing marine gene clusters. The first version contains information on clusters and the predicted molecules for over 500 marine-related prokaryotes. The user-friendly interface allows scientists to easily search by species, cluster type or molecule and visualize the information in table format or graphical representation. Conclusions: This new online portal simplifies the exploration and comparison of gene clusters in marine species for scientists and assists in characterizing the bioactive molecules they produce. MariClus integrates data from public sources, like GenBank, MIBiG and PubChem, with genome mining results from antiSMASH. This allows users to access and analyze various aspects of marine natural product biosynthesis and diversity. Full article
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11 pages, 1719 KiB  
Article
Jejucarbosides B–E, Chlorinated Cycloaromatized Enediynes, from a Marine Streptomyces sp.
by Ji Hyeon Im, Yern-Hyerk Shin, Eun Seo Bae, Sang Kook Lee and Dong-Chan Oh
Mar. Drugs 2023, 21(7), 405; https://doi.org/10.3390/md21070405 - 18 Jul 2023
Cited by 1 | Viewed by 1449
Abstract
Four new chlorinated cycloaromatized enediyne compounds, jejucarbosides B–E (14), were discovered together with previously-identified jejucarboside A from a marine actinomycete strain. Compounds 14 were identified as new chlorinated cyclopenta[a]indene glycosides based on 1D and 2D [...] Read more.
Four new chlorinated cycloaromatized enediyne compounds, jejucarbosides B–E (14), were discovered together with previously-identified jejucarboside A from a marine actinomycete strain. Compounds 14 were identified as new chlorinated cyclopenta[a]indene glycosides based on 1D and 2D nuclear magnetic resonance, high-resolution mass spectrometry, and circular dichroism (CD) spectra. Jejucarbosides B and E bear a carbonate functional group whereas jejucarbosides C and D are variants possessing 1,2-diol by losing the carbonate functionality. It is proposed that the production of 14 occurs via Bergman cycloaromatization capturing Cl- and H+ in the alternative positions of a p-benzyne intermediate derived from a 9-membered enediyne core. Jejucarboside E (4) displayed significant cytotoxicity against human cancer cell lines including SNU-638, SK-HEP-1, A549, HCT116, and MDA-MB-231, with IC50 values of 0.31, 0.40, 0.25, 0.29, and 0.48 μM, respectively, while jejucarbosides B–D (13) showed moderate or no cytotoxic effects. Full article
(This article belongs to the Special Issue Marine Drug Research in Korea II)
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14 pages, 2602 KiB  
Article
Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium
by Min Cheol Kim, Jaclyn M. Winter, Reiko Cullum, Alexander J. Smith and William Fenical
Mar. Drugs 2023, 21(6), 367; https://doi.org/10.3390/md21060367 - 20 Jun 2023
Viewed by 1570
Abstract
Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult [...] Read more.
Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult undertakings in natural products chemistry, and in most cases, the use of X-ray diffraction methods and total synthesis have been the major methods of assigning their absolute configurations. More recently, however, it has become apparent that the integration of bioinformatic data is growing in utility to assign absolute configurations. Genome mining and bioinformatic analysis identified the 97 kb mld biosynthetic cluster harboring seven type I polyketide synthases. A detailed bioinformatic investigation of the ketoreductase and enoylreductase domains within the multimodular polyketide synthases, coupled with NMR and X-ray diffraction data, allowed for the absolute configurations of marinolides A and B to be determined. While using bioinformatics to assign the relative and absolute configurations of natural products has high potential, this method must be coupled with full NMR-based analysis to both confirm bioinformatic assignments as well as any additional modifications that occur during biosynthesis. Full article
(This article belongs to the Special Issue 20 Years Commemorative Issue in Honor of Professor Paul J. Scheuer)
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11 pages, 1223 KiB  
Article
Sesquiterpenes from Streptomyces qinglanensis and Their Cytotoxic Activity
by Cao Van Anh, Jong Soon Kang, Jeong-Wook Yang, Joo-Hee Kwon, Chang-Su Heo, Hwa-Sun Lee, Chan Hong Park and Hee Jae Shin
Mar. Drugs 2023, 21(6), 361; https://doi.org/10.3390/md21060361 - 16 Jun 2023
Cited by 1 | Viewed by 1510
Abstract
Nine sesquiterpenes, including eight pentalenenes (18) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. [...] Read more.
Nine sesquiterpenes, including eight pentalenenes (18) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. Their planar structures were determined by spectroscopic methods (HRMS, 1D, and 2D NMR), and the absolute configuration was established by biosynthesis consideration and electronic-circular-dichroism (ECD) calculations. All the isolated compounds were screened for their cytotoxicity against six solid and seven blood cancer cell lines. Compounds 46 and 8 showed a moderate activity against all of the tested solid cell lines, with GI50 values ranging from 1.97 to 3.46 µM. Full article
(This article belongs to the Special Issue Marine Drug Research in Korea II)
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68 pages, 7649 KiB  
Review
Cyanobacteria: A Promising Source of Antifungal Metabolites
by Samuel Cavalcante do Amaral, Luciana Pereira Xavier, Vítor Vasconcelos and Agenor Valadares Santos
Mar. Drugs 2023, 21(6), 359; https://doi.org/10.3390/md21060359 - 14 Jun 2023
Cited by 1 | Viewed by 5275
Abstract
Cyanobacteria are a rich source of secondary metabolites, and they have received a great deal of attention due to their applicability in different industrial sectors. Some of these substances are known for their notorious ability to inhibit fungal growth. Such metabolites are very [...] Read more.
Cyanobacteria are a rich source of secondary metabolites, and they have received a great deal of attention due to their applicability in different industrial sectors. Some of these substances are known for their notorious ability to inhibit fungal growth. Such metabolites are very chemically and biologically diverse. They can belong to different chemical classes, including peptides, fatty acids, alkaloids, polyketides, and macrolides. Moreover, they can also target different cell components. Filamentous cyanobacteria have been the main source of these compounds. This review aims to identify the key features of these antifungal agents, as well as the sources from which they are obtained, their major targets, and the environmental factors involved when they are being produced. For the preparation of this work, a total of 642 documents dating from 1980 to 2022 were consulted, including patents, original research, review articles, and theses. Full article
(This article belongs to the Section Marine Pharmacology)
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21 pages, 1939 KiB  
Article
Pentaketides and 5-p-Hydroxyphenyl-2-pyridone Derivative from the Culture Extract of a Marine Sponge-Associated Fungus Hamigera avellanea KUFA0732
by Rotchana Klaram, Tida Dethoup, Fátima P. Machado, Luís Gales, Decha Kumla, Salar Hafez Ghoran, Emília Sousa, Sharad Mistry, Artur M. S. Silva and Anake Kijjoa
Mar. Drugs 2023, 21(6), 344; https://doi.org/10.3390/md21060344 - 2 Jun 2023
Cited by 2 | Viewed by 1628
Abstract
Five undescribed pentaketide derivatives, (R)-6,8-dihydroxy-4,5-dimethyl-3-methylidene-3,4-dihydro-1H-2-benzopyran-1-one (1), [(3S,4R)-3,8-dihydroxy-6-methoxy-4,5-dimethyl-1-oxo-3,4-dihydro-1H-isochromen-3-yl]methyl acetate (2), (R)-5, 7-dimethoxy-3-((S)-(1-hydroxyethyl)-3,4-dimethylisobenzofuran-1(3H)-one (4b), (S)-7-hydroxy-3-((S)-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran 1(3H)-one ( [...] Read more.
Five undescribed pentaketide derivatives, (R)-6,8-dihydroxy-4,5-dimethyl-3-methylidene-3,4-dihydro-1H-2-benzopyran-1-one (1), [(3S,4R)-3,8-dihydroxy-6-methoxy-4,5-dimethyl-1-oxo-3,4-dihydro-1H-isochromen-3-yl]methyl acetate (2), (R)-5, 7-dimethoxy-3-((S)-(1-hydroxyethyl)-3,4-dimethylisobenzofuran-1(3H)-one (4b), (S)-7-hydroxy-3-((S)-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran 1(3H)-one (5), and a p-hydroxyphenyl-2-pyridone derivative, avellaneanone (6), were isolated together with the previously reported (R)-3-acetyl-7-hydroxy-5-methoxy-3,4-dimethylisobenzofuran-1(3H)-one (3), (R)-7-hydroxy-3-((S)-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran-1(3H)-one (4a) and isosclerone (7), from the ethyl acetate extract of a culture of a marine sponge-derived fungus, Hamigera avellanea KUFA0732. The structures of the undescribed compounds were elucidated using 1D and 2D NMR, as well as high-resolution mass spectral analyses. The absolute configurations of the stereogenic carbons in 1, 4b, 5, and 6 were established by X-ray crystallographic analysis. The absolute configurations of C-3 and C-4 in 2 were determined by ROESY correlations and on the basis of their common biosynthetic origin with 1. The crude fungal extract and the isolated compounds 1, 3, 4b, 5, 6, and 7 were assayed for their growth inhibitory activity against various plant pathogenic fungi viz. Alternaria brassicicola, Bipolaris oryzae, Colletotrichum capsici, C. gloeosporiodes, Curvularia oryzae, Fusarium semitectum, Lasiodiplodia theobromae, Phytophthora palmivora, Pyricularia oryzae, Rhizoctonia oryzae and Sclerotium rolfsii. Full article
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11 pages, 1026 KiB  
Article
Synthesis and Antimalarial Evaluation of Halogenated Analogues of Thiaplakortone A
by Folake A. Egbewande, Brett D. Schwartz, Sandra Duffy, Vicky M. Avery and Rohan A. Davis
Mar. Drugs 2023, 21(5), 317; https://doi.org/10.3390/md21050317 - 22 May 2023
Viewed by 1436
Abstract
The incorporation of bromine, iodine or fluorine into the tricyclic core structure of thiaplakortone A (1), a potent antimalarial marine natural product, is reported. Although yields were low, it was possible to synthesise a small nine-membered library using the previously synthesised [...] Read more.
The incorporation of bromine, iodine or fluorine into the tricyclic core structure of thiaplakortone A (1), a potent antimalarial marine natural product, is reported. Although yields were low, it was possible to synthesise a small nine-membered library using the previously synthesised Boc-protected thiaplakortone A (2) as a scaffold for late-stage functionalisation. The new thiaplakortone A analogues (311) were generated using N-bromosuccinimide, N-iodosuccinimide or a Diversinate™ reagent. The chemical structures of all new analogues were fully characterised by 1D/2D NMR, UV, IR and MS data analyses. All compounds were evaluated for their antimalarial activity against Plasmodium falciparum 3D7 (drug-sensitive) and Dd2 (drug-resistant) strains. Incorporation of halogens at positions 2 and 7 of the thiaplakortone A scaffold was shown to reduce antimalarial activity compared to the natural product. Of the new compounds, the mono-brominated analogue (compound 5) displayed the best antimalarial activity with IC50 values of 0.559 and 0.058 μM against P. falciparum 3D7 and Dd2, respectively, with minimal toxicity against a human cell line (HEK293) observed at 80 μM. Of note, the majority of the halogenated compounds showed greater efficacy against the P. falciparum drug-resistant strain. Full article
(This article belongs to the Special Issue Marine Antiparasitic Agents)
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66 pages, 7625 KiB  
Review
Advanced Methods for Natural Products Discovery: Bioactivity Screening, Dereplication, Metabolomics Profiling, Genomic Sequencing, Databases and Informatic Tools, and Structure Elucidation
by Susana P. Gaudêncio, Engin Bayram, Lada Lukić Bilela, Mercedes Cueto, Ana R. Díaz-Marrero, Berat Z. Haznedaroglu, Carlos Jimenez, Manolis Mandalakis, Florbela Pereira, Fernando Reyes and Deniz Tasdemir
Mar. Drugs 2023, 21(5), 308; https://doi.org/10.3390/md21050308 - 19 May 2023
Cited by 20 | Viewed by 10359
Abstract
Natural Products (NP) are essential for the discovery of novel drugs and products for numerous biotechnological applications. The NP discovery process is expensive and time-consuming, having as major hurdles dereplication (early identification of known compounds) and structure elucidation, particularly the determination of the [...] Read more.
Natural Products (NP) are essential for the discovery of novel drugs and products for numerous biotechnological applications. The NP discovery process is expensive and time-consuming, having as major hurdles dereplication (early identification of known compounds) and structure elucidation, particularly the determination of the absolute configuration of metabolites with stereogenic centers. This review comprehensively focuses on recent technological and instrumental advances, highlighting the development of methods that alleviate these obstacles, paving the way for accelerating NP discovery towards biotechnological applications. Herein, we emphasize the most innovative high-throughput tools and methods for advancing bioactivity screening, NP chemical analysis, dereplication, metabolite profiling, metabolomics, genome sequencing and/or genomics approaches, databases, bioinformatics, chemoinformatics, and three-dimensional NP structure elucidation. Full article
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14 pages, 1600 KiB  
Article
Isolation of Nocuolin A and Synthesis of New Oxadiazine Derivatives. Design, Synthesis, Molecular Docking, Apoptotic Evaluation, and Cathepsin B Inhibition
by Víctor Tena Pérez, Luis Apaza Ticona, Alfredo H. Cabanillas, Santiago Maderuelo Corral, Diego Fernando Rosero Valencia, Antera Martel Quintana, Montserrat Ortega Domenech and Ángel Rumbero Sánchez
Mar. Drugs 2023, 21(5), 284; https://doi.org/10.3390/md21050284 - 29 Apr 2023
Cited by 1 | Viewed by 1399
Abstract
Nocuolin A (1), an oxadiazine, was isolated from the cyanobacterium Nostoc sp. Its chemical structure was elucidated using NMR and mass spectroscopic data. From this compound, two new oxadiazines, 3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropyl acetate (2) and 4-{3-[(6R [...] Read more.
Nocuolin A (1), an oxadiazine, was isolated from the cyanobacterium Nostoc sp. Its chemical structure was elucidated using NMR and mass spectroscopic data. From this compound, two new oxadiazines, 3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropyl acetate (2) and 4-{3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropoxy}-4-oxobutanoic acid (3), were synthesised. The chemical structures of these two compounds were elucidated by a combination of NMR and MS analysis. Compound 3 showed cytotoxicity against the ACHN (0.73 ± 0.10 μM) and Hepa-1c1c7 (0.91 ± 0.08 μM) tumour cell lines. Similarly, compound 3 significantly decreased cathepsin B activity in ACHN and Hepa-1c1c7 tumour cell lines at concentrations of 1.52 ± 0.13 nM and 1.76 ± 0.24 nM, respectively. In addition, compound 3 showed no in vivo toxicity in a murine model treated with a dose of 4 mg/kg body weight. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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15 pages, 1883 KiB  
Article
Enhanced Molecular Networking Shows Microbacterium sp. V1 as a Factory of Antioxidant Proline-Rich Peptides
by Giovanni Andrea Vitale, Silvia Scarpato, Alfonso Mangoni, Maria Valeria D’Auria, Gerardo Della Sala and Donatella de Pascale
Mar. Drugs 2023, 21(4), 256; https://doi.org/10.3390/md21040256 - 21 Apr 2023
Cited by 3 | Viewed by 2902
Abstract
Two linear proline-rich peptides (12), bearing an N-terminal pyroglutamate, were isolated from the marine bacterium Microbacterium sp. V1, associated with the marine sponge Petrosia ficiformis, collected in the volcanic CO2 vents in Ischia Island (South Italy). Peptide [...] Read more.
Two linear proline-rich peptides (12), bearing an N-terminal pyroglutamate, were isolated from the marine bacterium Microbacterium sp. V1, associated with the marine sponge Petrosia ficiformis, collected in the volcanic CO2 vents in Ischia Island (South Italy). Peptide production was triggered at low temperature following the one strain many compounds (OSMAC) method. Both peptides were detected together with other peptides (38) via an integrated, untargeted MS/MS-based molecular networking and cheminformatic approach. The planar structure of the peptides was determined by extensive 1D and 2D NMR and HR-MS analysis, and the stereochemistry of the aminoacyl residues was inferred by Marfey’s analysis. Peptides 18 are likely to arise from Microbacterium V1 tailor-made proteolysis of tryptone. Peptides 1 and 2 were shown to display antioxidant properties in the ferric-reducing antioxidant power (FRAP) assay. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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18 pages, 2603 KiB  
Article
Challenging Structure Elucidation of Lumnitzeralactone, an Ellagic Acid Derivative from the Mangrove Lumnitzera racemosa
by Jonas Kappen, Jeprianto Manurung, Tristan Fuchs, Sahithya Phani Babu Vemulapalli, Lea M. Schmitz, Andrej Frolov, Andria Agusta, Alexandra N. Muellner-Riehl, Christian Griesinger, Katrin Franke and Ludger A. Wessjohann
Mar. Drugs 2023, 21(4), 242; https://doi.org/10.3390/md21040242 - 14 Apr 2023
Viewed by 3838
Abstract
The previously undescribed natural product lumnitzeralactone (1), which represents a derivative of ellagic acid, was isolated from the anti-bacterial extract of the Indonesian mangrove species Lumnitzera racemosa Willd. The structure of lumnitzeralactone (1), a proton-deficient and highly challenging condensed [...] Read more.
The previously undescribed natural product lumnitzeralactone (1), which represents a derivative of ellagic acid, was isolated from the anti-bacterial extract of the Indonesian mangrove species Lumnitzera racemosa Willd. The structure of lumnitzeralactone (1), a proton-deficient and highly challenging condensed aromatic ring system, was unambiguously elucidated by extensive spectroscopic analyses involving high-resolution mass spectrometry (HRMS), 1D 1H and 13C nuclear magnetic resonance spectroscopy (NMR), and 2D NMR (including 1,1-ADEQUATE and 1,n-ADEQUATE). Determination of the structure was supported by computer-assisted structure elucidation (CASE system applying ACD-SE), density functional theory (DFT) calculations, and a two-step chemical synthesis. Possible biosynthetic pathways involving mangrove-associated fungi have been suggested. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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32 pages, 761 KiB  
Review
Applications of Antioxidant Secondary Metabolites of Sargassum spp.
by Marcelo D. Catarino, Rita Silva-Reis, Amina Chouh, Sónia Silva, Susana S. Braga, Artur M. S. Silva and Susana M. Cardoso
Mar. Drugs 2023, 21(3), 172; https://doi.org/10.3390/md21030172 - 9 Mar 2023
Cited by 10 | Viewed by 6524
Abstract
Sargassum is one of the largest and most diverse genus of brown seaweeds, comprising of around 400 taxonomically accepted species. Many species of this genus have long been a part of human culture with applications as food, feed, and remedies in folk medicine. [...] Read more.
Sargassum is one of the largest and most diverse genus of brown seaweeds, comprising of around 400 taxonomically accepted species. Many species of this genus have long been a part of human culture with applications as food, feed, and remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of natural antioxidant compounds of great interest, including polyphenols, carotenoids, meroterpenoids, phytosterols, and several others. Such compounds provide a valuable contribution to innovation that can translate, for instance, into the development of new ingredients for preventing product deterioration, particularly in food products, cosmetics or biostimulants to boost crops production and tolerance to abiotic stress. This manuscript revises the chemical composition of Sargassum seaweeds, highlighting their antioxidant secondary metabolites, their mechanism of action, and multiple applications in fields, including agriculture, food, and health. Full article
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18 pages, 4780 KiB  
Article
Marinobazzanan, a Bazzanane-Type Sesquiterpenoid, Suppresses the Cell Motility and Tumorigenesis in Cancer Cells
by Sultan Pulat, Prima F. Hillman, Sojeong Kim, Ratnakar N. Asolkar, Haerin Kim, Rui Zhou, İsa Taş, Chathurika D. B. Gamage, Mücahit Varlı, So-Yeon Park, Sung Chul Park, Inho Yang, Jongheon Shin, Dong-Chan Oh, Hangun Kim, Sang-Jip Nam and William Fenical
Mar. Drugs 2023, 21(3), 153; https://doi.org/10.3390/md21030153 - 25 Feb 2023
Cited by 5 | Viewed by 2401
Abstract
Marinobazzanan (1), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was elucidated using NMR and mass spectroscopic data, while the relative configurations were established through the analysis of [...] Read more.
Marinobazzanan (1), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was elucidated using NMR and mass spectroscopic data, while the relative configurations were established through the analysis of NOESY data. The absolute configurations of 1 were determined by the modified Mosher’s method as well as vibrational circular dichroism (VCD) spectra calculation and it was determined as 6R, 7R, 9R, and 10R. It was found that compound 1 was not cytotoxic to human cancer cells, including A549 (lung cancer), AGS (gastric cancer), and Caco-2 (colorectal cancer) below the concentration of 25 μM. However, compound 1 was shown to significantly decrease cancer-cell migration and invasion and soft-agar colony-formation ability at concentrations ranging from 1 to 5 μM by downregulating the expression level of KITENIN and upregulating the expression level of KAI1. Compound 1 suppressed β-catenin-mediated TOPFLASH activity and its downstream targets in AGS, A549, and Caco-2 and slightly suppressed the Notch signal pathway in three cancer cells. Furthermore, 1 also reduced the number of metastatic nodules in an intraperitoneal xenograft mouse model. Full article
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18 pages, 2608 KiB  
Article
Bioactive Oxylipins Profile in Marine Microalgae
by Amandyne Linares-Maurizi, Guillaume Reversat, Rana Awad, Valérie Bultel-Poncé, Camille Oger, Jean-Marie Galano, Laurence Balas, Anaelle Durbec, Justine Bertrand-Michel, Thierry Durand, Rémi Pradelles and Claire Vigor
Mar. Drugs 2023, 21(3), 136; https://doi.org/10.3390/md21030136 - 22 Feb 2023
Cited by 6 | Viewed by 5281
Abstract
Microalgae are photosynthetic microscopic organisms that serve as the primary food source in aquatic environments. Microalgae can synthesize a wide variety of molecules, such as polyunsaturated fatty acids (PUFAs) of the omega-3 and omega-6 series. Oxidative degradation of PUFA due to radical and/or [...] Read more.
Microalgae are photosynthetic microscopic organisms that serve as the primary food source in aquatic environments. Microalgae can synthesize a wide variety of molecules, such as polyunsaturated fatty acids (PUFAs) of the omega-3 and omega-6 series. Oxidative degradation of PUFA due to radical and/or enzymatic conversion leads to the formation of oxylipins, which are compounds known for their bioactive properties. In the present study, we aim to profile oxylipins from five microalgae species grown in 10-L photo-bioreactors under optimal conditions. During their exponential phase, microalgae were harvested, extracted and analyzed by LC-MS/MS to determine the qualitative and quantitative profile of oxylipins for each species. The five different selected microalgae revealed a high diversity of metabolites, up to 33 non-enzymatic and 24 enzymatic oxylipins present in different concentrations. Taken together, these findings highlight an interesting role of marine microalgae as a source of bioactive lipids mediators, which we hypothesize have an important function in preventive health measures such as amelioration of inflammation. The rich mixture of oxylipins may display advantages to biological organisms, especially by providing for human health benefits including antioxidant, anti-inflammatory, neuroprotective or immunomodulator activities. Some oxylipins are also well known for their cardiovascular properties. Full article
(This article belongs to the Special Issue Marine-Derived Compounds Applied in Cardiovascular Disease)
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21 pages, 4498 KiB  
Review
Marine Organisms as a Prolific Source of Bioactive Depsipeptides
by Mingyuan Zeng, Jianyun Tao, Shuang Xu, Xuelian Bai and Huawei Zhang
Mar. Drugs 2023, 21(2), 120; https://doi.org/10.3390/md21020120 - 11 Feb 2023
Cited by 8 | Viewed by 1982
Abstract
Depsipeptides, an important group of polypeptides containing residues of hydroxy acids and amino acids linked together by amide and ester bonds, have potential applications in agriculture and medicine. A growing body of evidence demonstrates that marine organisms are prolific sources of depsipeptides, such [...] Read more.
Depsipeptides, an important group of polypeptides containing residues of hydroxy acids and amino acids linked together by amide and ester bonds, have potential applications in agriculture and medicine. A growing body of evidence demonstrates that marine organisms are prolific sources of depsipeptides, such as marine cyanobacteria, sponges, mollusks, microorganisms and algae. However, these substances have not yet been comprehensively summarized. In order to enrich our knowledge about marine depsipeptides, their biological sources and structural features, as well as bioactivities, are highlighted in this review after an extensive literature search and data analysis. Full article
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13 pages, 562 KiB  
Article
New Nostocyclophanes from Nostoc linckia
by Jingqiu Dai, Casey S. Philbin, Clay Wakano, Wesley Y. Yoshida and Philip G. Williams
Mar. Drugs 2023, 21(2), 101; https://doi.org/10.3390/md21020101 - 31 Jan 2023
Cited by 4 | Viewed by 4052
Abstract
Six new nostocyclophanes and four known compounds have been isolated from Nostoc linckia (Nostocaceae) cyanobacterial strain UTEX B1932. The new compounds, nostocyclophanes E–J (16), were characterized by NMR and MS techniques. The known compounds were nostocyclophanes B–D, previously isolated [...] Read more.
Six new nostocyclophanes and four known compounds have been isolated from Nostoc linckia (Nostocaceae) cyanobacterial strain UTEX B1932. The new compounds, nostocyclophanes E–J (16), were characterized by NMR and MS techniques. The known compounds were nostocyclophanes B–D, previously isolated from this strain, and dedichloronostocyclophane D. Structural modifications on the new [7.7]paracyclophane analogs 15, isolated from the 80% methanol fraction, range from simple changes such as the lack of methylation or halogenation to more unusual modifications such as those seen in nostocyclophane H (4), in which the exocyclic alkyl chains are of different length; this is the first time this modification has been observed in this family of natural products. In addition, nostocyclophane J (6) is a linear analog in which C-20 is chlorinated in preparation for the presumed enzymatic Friedel–Craft cyclization needed to form the final ring structure, analogous to the biosynthesis of the related cylindrocyclophanes. Nostocyclophane D, dedichloronostocyclophane D, and nostocyclophanes E-J demonstrated moderate to weak growth inhibition against MDA-MB-231 breast cancer cells. Full article
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15 pages, 3925 KiB  
Review
Marine Natural and Nature-Inspired Compounds Targeting Peroxisome Proliferator Activated Receptors (PPARs)
by Enrico D’Aniello, Pietro Amodeo and Rosa Maria Vitale
Mar. Drugs 2023, 21(2), 89; https://doi.org/10.3390/md21020089 - 26 Jan 2023
Cited by 3 | Viewed by 3360
Abstract
Peroxisome proliferator-activated receptors α, γ and β/δ (PPARα, PPARγ, and PPARβ/δ) are a family of ligand-activated transcriptional factors belonging to the superfamily of nuclear receptors regulating the expression of genes involved in lipid and carbohydrate metabolism, energy homeostasis, inflammation, and the immune response. [...] Read more.
Peroxisome proliferator-activated receptors α, γ and β/δ (PPARα, PPARγ, and PPARβ/δ) are a family of ligand-activated transcriptional factors belonging to the superfamily of nuclear receptors regulating the expression of genes involved in lipid and carbohydrate metabolism, energy homeostasis, inflammation, and the immune response. For this reason, they represent attractive targets for the treatment of a variety of metabolic diseases and, more recently, for neurodegenerative disorders due to their emerging neuroprotective effects. The degree of activation, from partial to full, along with the selectivity toward the different isoforms, greatly affect the therapeutic efficacy and the safety profile of PPAR agonists. Thus, there is a high interest toward novel scaffolds with proper combinations of activity and selectivity. This review intends to provide an overview of the discovery, optimization, and structure–activity relationship studies on PPAR modulators from marine sources, along with the structural and computational studies that led to their identification and/or elucidation, and rationalization of their mechanisms of action. Full article
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30 pages, 2013 KiB  
Review
Promising Antiparasitic Natural and Synthetic Products from Marine Invertebrates and Microorganisms
by Mingyue Zhang, Qinrong Zhang, Qunde Zhang, Xinyuan Cui and Lifeng Zhu
Mar. Drugs 2023, 21(2), 84; https://doi.org/10.3390/md21020084 - 25 Jan 2023
Cited by 4 | Viewed by 2566
Abstract
Parasitic diseases still threaten human health. At present, a number of parasites have developed drug resistance, and it is urgent to find new and effective antiparasitic drugs. As a rich source of biological compounds, marine natural products have been increasingly screened as candidates [...] Read more.
Parasitic diseases still threaten human health. At present, a number of parasites have developed drug resistance, and it is urgent to find new and effective antiparasitic drugs. As a rich source of biological compounds, marine natural products have been increasingly screened as candidates for developing new antiparasitic drugs. The literature related to the study of the antigenic animal activity of marine natural compounds from invertebrates and microorganisms was selected to summarize the research progress of marine compounds and the structure–activity relationship of these compounds in the past five years and to explore the possible sources of potential antiparasitic drugs for parasite treatment. Full article
(This article belongs to the Special Issue Marine Antiparasitic Agents)
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15 pages, 2339 KiB  
Article
Secondary Metabolites with Anti-Inflammatory Activity from Laurencia majuscula Collected in the Red Sea
by Mohamed A. Tammam, Maria G. Daskalaki, Nikolaos Tsoureas, Ourania Kolliniati, Aldoushy Mahdy, Sotirios C. Kampranis, Christos Tsatsanis, Vassilios Roussis and Efstathia Ioannou
Mar. Drugs 2023, 21(2), 79; https://doi.org/10.3390/md21020079 - 24 Jan 2023
Cited by 4 | Viewed by 3951
Abstract
The chemical investigation of the organic extract of the red alga Laurencia majuscula collected from Hurghada reef in the Red Sea resulted in the isolation of five C15 acetogenins, including four tricyclic ones of the maneonene type (14) [...] Read more.
The chemical investigation of the organic extract of the red alga Laurencia majuscula collected from Hurghada reef in the Red Sea resulted in the isolation of five C15 acetogenins, including four tricyclic ones of the maneonene type (14) and a 5-membered one (5), 15 sesquiterpenes, including seven lauranes (612), one cuparane (13), one seco-laurane (14), one snyderane (15), two chamigranes (16, 17), two rearranged chamigranes (18, 19) and one aristolane (20), as well as a tricyclic diterpene (21) and a chlorinated fatty acid derivative (22). Among them, compounds 13, 5, 7, 8, 10, 11 and 14 are new natural products. The structures and the relative configurations of the isolated natural products have been established based on extensive analysis of their NMR and MS data, while the absolute configuration of maneonenes F (1) and G (2) was determined on the basis of single-crystal X-ray diffraction analysis. The anti-inflammatory activity of compounds 1, 2, 48, 10, 1216, 18 and 2022 was evaluated by measuring suppression of nitric oxide (NO) release in TLR4-activated RAW 264.7 macrophages in culture. All compounds, except 6, exhibited significant anti-inflammatory activity. Among them, metabolites 1, 4 and 18 did not exhibit any cytostatic activity at the tested concentrations. The most prominent anti-inflammatory activity, accompanied by absence of cytostatic activity at the same concentration, was exerted by compounds 5 and 18, with IC50 values of 3.69 μM and 3.55 μΜ, respectively. Full article
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18 pages, 2998 KiB  
Article
Cryptic Diversity of Black Band Disease Cyanobacteria in Siderastrea siderea Corals Revealed by Chemical Ecology and Comparative Genome-Resolved Metagenomics
by Julie L. Meyer, Sarath P. Gunasekera, Anya L. Brown, Yousong Ding, Stephanie Miller, Max Teplitski and Valerie J. Paul
Mar. Drugs 2023, 21(2), 76; https://doi.org/10.3390/md21020076 - 22 Jan 2023
Cited by 6 | Viewed by 4307
Abstract
Black band disease is a globally distributed and easily recognizable coral disease. Despite years of study, the etiology of this coral disease, which impacts dozens of stony coral species, is not completely understood. Although black band disease mats are predominantly composed of the [...] Read more.
Black band disease is a globally distributed and easily recognizable coral disease. Despite years of study, the etiology of this coral disease, which impacts dozens of stony coral species, is not completely understood. Although black band disease mats are predominantly composed of the cyanobacterial species Roseofilum reptotaenium, other filamentous cyanobacterial strains and bacterial heterotrophs are readily detected. Through chemical ecology and metagenomic sequencing, we uncovered cryptic strains of Roseofilum species from Siderastrea siderea corals that differ from those on other corals in the Caribbean and Pacific. Isolation of metabolites from Siderastrea-derived Roseofilum revealed the prevalence of unique forms of looekeyolides, distinct from previously characterized Roseofilum reptotaenium strains. In addition, comparative genomics of Roseofilum strains showed that only Siderastrea-based Roseofilum strains have the genetic capacity to produce lasso peptides, a family of compounds with diverse biological activity. All nine Roseofilum strains examined here shared the genetic capacity to produce looekeyolides and malyngamides, suggesting these compounds support the ecology of this genus. Similar biosynthetic gene clusters are not found in other cyanobacterial genera associated with black band disease, which may suggest that looekeyolides and malyngamides contribute to disease etiology through yet unknown mechanisms. Full article
(This article belongs to the Special Issue Reef Ecology and Marine Drug Discovery)
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19 pages, 17326 KiB  
Article
Botryllin, a Novel Antimicrobial Peptide from the Colonial Ascidian Botryllus schlosseri
by Nicola Franchi, Loriano Ballarin and Francesca Cima
Mar. Drugs 2023, 21(2), 74; https://doi.org/10.3390/md21020074 - 21 Jan 2023
Cited by 6 | Viewed by 3081
Abstract
By mining the transcriptome of the colonial ascidian Botryllus schlosseri, we identified a transcript for a novel styelin-like antimicrobial peptide, which we named botryllin. The gene is constitutively transcribed by circulating cytotoxic morula cells (MCs) as a pre-propeptide that is then cleaved [...] Read more.
By mining the transcriptome of the colonial ascidian Botryllus schlosseri, we identified a transcript for a novel styelin-like antimicrobial peptide, which we named botryllin. The gene is constitutively transcribed by circulating cytotoxic morula cells (MCs) as a pre-propeptide that is then cleaved to mature peptide. The synthetic peptide, obtained from in silico translation of the transcript, shows robust killing activity of bacterial and unicellular yeast cells, causing breakages of both the plasma membrane and the cell wall. Specific monoclonal antibodies were raised against the epitopes of the putative amino acid sequence of the propeptide and the mature peptide; in both cases, they label the MC granular content. Upon MC degranulation induced by the presence of nonself, the antibodies recognise the extracellular nets with entrapped bacteria nearby MC remains. The obtained results suggest that the botryllin gene carries the information for the synthesis of an AMP involved in the protection of B. schlosseri from invading foreign cells. Full article
(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)
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14 pages, 3607 KiB  
Article
Molecular Networking Revealed Unique UV-Absorbing Phospholipids: Favilipids from the Marine Sponge Clathria faviformis
by Silvia Scarpato, Roberta Teta, Paola De Cicco, Francesca Borrelli, Joseph R. Pawlik, Valeria Costantino and Alfonso Mangoni
Mar. Drugs 2023, 21(2), 58; https://doi.org/10.3390/md21020058 - 18 Jan 2023
Cited by 2 | Viewed by 2905
Abstract
Analysis of extracts of the marine sponge Clathria faviformis by high-resolution LC-MS2 and molecular networking resulted in the discovery of a new family of potentially UV-protecting phospholipids, the favilipids. One of them, favilipid A (1), was isolated and its structure [...] Read more.
Analysis of extracts of the marine sponge Clathria faviformis by high-resolution LC-MS2 and molecular networking resulted in the discovery of a new family of potentially UV-protecting phospholipids, the favilipids. One of them, favilipid A (1), was isolated and its structure determined by mass and tandem mass spectrometry, NMR, electronic circular dichroism (ECD), and computational studies. Favilipid A, which has no close analogues among natural products, possesses an unprecedented structure characterized by a 4-aminodihydropiridinium core, resulting in UV-absorbing properties that are very unusual for a phospholipid. Consequently, favilipid A could inspire the development of a new class of molecules to be used as sunscreen ingredients. In addition, favilipid A inhibited by 58–48% three kinases (JAK3, IKKβ, and SYK) involved in the regulation of the immune system, suggesting a potential use for treatment of autoimmune diseases, hematologic cancers, and other inflammatory states. Full article
(This article belongs to the Special Issue Discovering Marine Bioactive Compounds by Molecular Networking)
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26 pages, 2681 KiB  
Review
Secondary Metabolites from Marine-Derived Bacteria with Antibiotic and Antibiofilm Activities against Drug-Resistant Pathogens
by Joko Tri Wibowo, Asep Bayu, Widya Dwi Aryati, Carla Fernandes, Arry Yanuar, Anake Kijjoa and Masteria Yunovilsa Putra
Mar. Drugs 2023, 21(1), 50; https://doi.org/10.3390/md21010050 - 12 Jan 2023
Cited by 9 | Viewed by 4316
Abstract
The search for new antibiotics against drug-resistant microbes has been expanded to marine bacteria. Marine bacteria have been proven to be a prolific source of a myriad of novel compounds with potential biological activities. Therefore, this review highlights novel and bioactive compounds from [...] Read more.
The search for new antibiotics against drug-resistant microbes has been expanded to marine bacteria. Marine bacteria have been proven to be a prolific source of a myriad of novel compounds with potential biological activities. Therefore, this review highlights novel and bioactive compounds from marine bacteria reported during the period of January 2016 to December 2021. Published articles containing novel marine bacterial secondary metabolites that are active against drug-resistant pathogens were collected. Previously described compounds (prior to January 2016) are not included in this review. Unreported compounds during this period that exhibited activity against pathogenic microbes were discussed and compared in order to find the cue of the structure–bioactivity relationship. The results showed that Streptomyces are the most studied bacteria with undescribed bioactive compounds, followed by other genera in the Actinobacteria. We have categorized the structures of the compounds in the present review into four groups, based on their biosynthetic origins, as polyketide derivatives, amino acid derivatives, terpenoids, as well as compounds with mixed origin. These compounds were active against one or more drug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant Enterococci (VRE), multidrug-resistant Mycobacterium tuberculosis (MDR-TB), and amphotericin B-resistant Candida albicans. In addition, some of the compounds also showed activity against biofilm formation of the test bacteria. Some previously undescribed compounds, isolated from marine-derived bacteria during this period, could have a good potential as lead compounds for the development of drug candidates to overcome multidrug-resistant pathogens. Full article
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28 pages, 6086 KiB  
Article
Marine Sponge and Octocoral-Associated Bacteria Show Versatile Secondary Metabolite Biosynthesis Potential and Antimicrobial Activities against Human Pathogens
by João F. Almeida, Matilde Marques, Vanessa Oliveira, Conceição Egas, Dalila Mil-Homens, Romeu Viana, Daniel F. R. Cleary, Yusheng M. Huang, Arsénio M. Fialho, Miguel C. Teixeira, Newton C. M. Gomes, Rodrigo Costa and Tina Keller-Costa
Mar. Drugs 2023, 21(1), 34; https://doi.org/10.3390/md21010034 - 30 Dec 2022
Cited by 5 | Viewed by 4562
Abstract
Marine microbiomes are prolific sources of bioactive natural products of potential pharmaceutical value. This study inspected two culture collections comprising 919 host-associated marine bacteria belonging to 55 genera and several thus-far unclassified lineages to identify isolates with potentially rich secondary metabolism and antimicrobial [...] Read more.
Marine microbiomes are prolific sources of bioactive natural products of potential pharmaceutical value. This study inspected two culture collections comprising 919 host-associated marine bacteria belonging to 55 genera and several thus-far unclassified lineages to identify isolates with potentially rich secondary metabolism and antimicrobial activities. Seventy representative isolates had their genomes mined for secondary metabolite biosynthetic gene clusters (SM-BGCs) and were screened for antimicrobial activities against four pathogenic bacteria and five pathogenic Candida strains. In total, 466 SM-BGCs were identified, with antimicrobial peptide- and polyketide synthase-related SM-BGCs being frequently detected. Only 38 SM-BGCs had similarities greater than 70% to SM-BGCs encoding known compounds, highlighting the potential biosynthetic novelty encoded by these genomes. Cross-streak assays showed that 33 of the 70 genome-sequenced isolates were active against at least one Candida species, while 44 isolates showed activity against at least one bacterial pathogen. Taxon-specific differences in antimicrobial activity among isolates suggested distinct molecules involved in antagonism against bacterial versus Candida pathogens. The here reported culture collections and genome-sequenced isolates constitute a valuable resource of understudied marine bacteria displaying antimicrobial activities and potential for the biosynthesis of novel secondary metabolites, holding promise for a future sustainable production of marine drug leads. Full article
(This article belongs to the Special Issue Reef Ecology and Marine Drug Discovery)
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26 pages, 5346 KiB  
Review
Recent Advancement in Anticancer Compounds from Marine Organisms: Approval, Use and Bioinformatic Approaches to Predict New Targets
by Giovanna Santaniello, Angela Nebbioso, Lucia Altucci and Mariarosaria Conte
Mar. Drugs 2023, 21(1), 24; https://doi.org/10.3390/md21010024 - 28 Dec 2022
Cited by 4 | Viewed by 3907
Abstract
In recent years, the study of anticancer bioactive compounds from marine sources has received wide interest. Contextually, world regulatory authorities have approved several marine molecules, and new synthetic derivatives have also been synthesized and structurally improved for the treatment of numerous forms of [...] Read more.
In recent years, the study of anticancer bioactive compounds from marine sources has received wide interest. Contextually, world regulatory authorities have approved several marine molecules, and new synthetic derivatives have also been synthesized and structurally improved for the treatment of numerous forms of cancer. However, the administration of drugs in cancer patients requires careful evaluation since their interaction with individual biological macromolecules, such as proteins or nucleic acids, determines variable downstream effects. This is reflected in a constant search for personalized therapies that lay the foundations of modern medicine. The new knowledge acquired on cancer mechanisms has certainly allowed advancements in tumor prevention, but unfortunately, due to the huge complexity and heterogeneity of cancer, we are still looking for a definitive therapy and clinical approaches. In this review, we discuss the significance of recently approved molecules originating from the marine environment, starting from their organism of origin to their structure and mechanism of action. Subsequently, these bio-compounds are used as models to illustrate possible bioinformatics approaches for the search of new targets that are useful for improving the knowledge on anticancer therapies. Full article
(This article belongs to the Special Issue Bioinformatics of Marine Natural Products 2.0)
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17 pages, 641 KiB  
Article
Never, Ever Make an Enemy… Out of an Anemone: Transcriptomic Comparison of Clownfish Hosting Sea Anemone Venoms
by Alonso Delgado, Charlotte Benedict, Jason Macrander and Marymegan Daly
Mar. Drugs 2022, 20(12), 730; https://doi.org/10.3390/md20120730 - 23 Nov 2022
Cited by 8 | Viewed by 4128
Abstract
Sea anemones are predatory marine invertebrates and have diverse venom arsenals. Venom is integral to their biology, and is used in competition, defense, and feeding. Three lineages of sea anemones are known to have independently evolved symbiotic relationships with clownfish, however the evolutionary [...] Read more.
Sea anemones are predatory marine invertebrates and have diverse venom arsenals. Venom is integral to their biology, and is used in competition, defense, and feeding. Three lineages of sea anemones are known to have independently evolved symbiotic relationships with clownfish, however the evolutionary impact of this relationship on the venom composition of the host is still unknown. Here, we investigate the potential of this symbiotic relationship to shape the venom profiles of the sea anemones that host clownfish. We use transcriptomic data to identify differences and similarities in venom profiles of six sea anemone species, representing the three known clades of clownfish-hosting sea anemones. We recovered 1121 transcripts matching verified toxins across all species, and show that hemolytic and hemorrhagic toxins are consistently the most dominant and diverse toxins across all species examined. These results are consistent with the known biology of sea anemones, provide foundational data on venom diversity of these species, and allow for a review of existing hierarchical structures in venomic studies. Full article
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22 pages, 2920 KiB  
Article
A Metabolomics-Based Toolbox to Assess and Compare the Metabolic Potential of Unexplored, Difficult-to-Grow Bacteria
by Federica Fiorini, Felizitas Bajerski, Olga Jeske, Cendrella Lepleux, Jörg Overmann and Mark Brönstrup
Mar. Drugs 2022, 20(11), 713; https://doi.org/10.3390/md20110713 - 14 Nov 2022
Cited by 2 | Viewed by 2316
Abstract
Novel high-throughput cultivation techniques create a demand to pre-select strains for in-depth follow-up studies. We report a workflow to identify promising producers of novel natural products by systematically characterizing their metabolomes. For this purpose, 60 strains from four phyla (Proteobacteria, Bacteroidetes, Actinobacteria and [...] Read more.
Novel high-throughput cultivation techniques create a demand to pre-select strains for in-depth follow-up studies. We report a workflow to identify promising producers of novel natural products by systematically characterizing their metabolomes. For this purpose, 60 strains from four phyla (Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes) comprising 16 novel species and six novel genera were cultivated from marine and terrestrial sources. Their cellular metabolomes were recorded by LC-MS/MS; data analysis comprised databases MS/MS matching, in silico compound assignment, and GNPS-based molecular networking. Overall, 1052 different molecules were identified from 6418 features, among them were unusual metabolites such as 4-methoxychalcone. Only a minor portion of the 755 features were found in all phyla, while the majority occurred in a single phylogroup or even in a single strain. Metabolomic methods enabled the recognition of highly talented strains such as AEG42_45, which had 107 unique features, among which a family of 28 potentially novel and related compounds according to MS/MS similarities. In summary, we propose that high-throughput cultivation and isolation of bacteria in combination with the presented systematic and unbiased metabolome analysis workflow is a promising approach to capture and assess the enormous metabolic potential of previously uncultured bacteria. Full article
(This article belongs to the Special Issue Marine Metabolomics 2023)
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13 pages, 1141 KiB  
Article
Computational Metabolomics Tools Reveal Subarmigerides, Unprecedented Linear Peptides from the Marine Sponge Holobiont Callyspongia subarmigera
by Andrea Castaldi, Roberta Teta, Germana Esposito, Mehdi A. Beniddir, Nicole J. De Voogd, Sébastien Duperron, Valeria Costantino and Marie-Lise Bourguet-Kondracki
Mar. Drugs 2022, 20(11), 673; https://doi.org/10.3390/md20110673 - 27 Oct 2022
Cited by 2 | Viewed by 3854
Abstract
A detailed examination of a unique molecular family, restricted to the Callyspongia genus, in a molecular network obtained from an in-house Haplosclerida marine sponge collection (including Haliclona, Callyspongia, Xestospongia, and Petrosia species) led to the discovery of subarmigerides, a series [...] Read more.
A detailed examination of a unique molecular family, restricted to the Callyspongia genus, in a molecular network obtained from an in-house Haplosclerida marine sponge collection (including Haliclona, Callyspongia, Xestospongia, and Petrosia species) led to the discovery of subarmigerides, a series of rare linear peptides from Callyspongia subarmigera, a genus mainly known for polyacetylenes and lipids. The structure of the sole isolated peptide, subarmigeride A (1) was elucidated through extensive 1D and 2D NMR spectroscopy, HRMS/MS, and Marfey’s method to assign its absolute configuration. The putative structures of seven additional linear peptides were proposed by an analysis of their respective MS/MS spectra and a comparison of their fragmentation patterns with the heptapeptide 1. Surprisingly, several structurally related analogues of subarmigeride A (1) occurred in one distinct cluster from the molecular network of the cyanobacteria strains of the Guadeloupe mangroves, suggesting that the true producer of this peptide family might be the microbial sponge-associated community, i.e., the sponge-associated cyanobacteria. Full article
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32 pages, 9725 KiB  
Review
The Tetrahydrofuran Motif in Marine Lipids and Terpenes
by Paula González-Andrés, Laura Fernández-Peña, Carlos Díez-Poza and Asunción Barbero
Mar. Drugs 2022, 20(10), 642; https://doi.org/10.3390/md20100642 - 15 Oct 2022
Cited by 12 | Viewed by 2920
Abstract
Heterocycles are particularly common moieties within marine natural products. Specifically, tetrahydrofuranyl rings are present in a variety of compounds which present complex structures and interesting biological activities. Focusing on terpenoids, a high number of tetrahydrofuran-containing metabolites have been isolated during the last decades. [...] Read more.
Heterocycles are particularly common moieties within marine natural products. Specifically, tetrahydrofuranyl rings are present in a variety of compounds which present complex structures and interesting biological activities. Focusing on terpenoids, a high number of tetrahydrofuran-containing metabolites have been isolated during the last decades. They show promising biological activities, making them potential leads for novel antibiotics, antikinetoplastid drugs, amoebicidal substances, or anticancer drugs. Thus, they have attracted the attention of the synthetics community and numerous approaches to their total syntheses have appeared. Here, we offer the reader an overview of marine-derived terpenoids and related compounds, their isolation, structure determination, and a special focus on their total syntheses and biological profiles. Full article
(This article belongs to the Special Issue Heterocyclic Compounds from Marine Organisms)
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