Marine Drugs

15 pages, 1509 KiB

Open AccessArticle

Isoquinoline Alkaloids as Protein Tyrosine Phosphatase Inhibitors from a Deep-Sea-Derived Fungus Aspergillus puniceus

by Cheng-Mei Liu, Fei-Hua Yao, Xin-Hua Lu, Xue-Xia Zhang, Lian-Xiang Luo, Xiao Liang and Shu-Hua Qi

Mar. Drugs 2022, 20(1), 78; https://doi.org/10.3390/md20010078 - 17 Jan 2022

Cited by 15 | Viewed by 2493

Abstract

Puniceusines A–N (1–14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the [...] Read more.

Puniceusines A–N (1–14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the structures of 6 and 12 were further confirmed by a single-crystal X-ray diffraction analysis. Compounds 3–5 and 8–13 unprecedentedly contained an isoquinolinyl, a polysubstituted benzyl or a pyronyl at position C-7 of isoquinoline nucleus. Compounds 3 and 4 showed selective inhibitory activity against protein tyrosine phosphatase CD45 with IC₅₀ values of 8.4 and 5.6 µM, respectively, 4 also had a moderate cytotoxicity towards human lung adenocarcinoma cell line H1975 with an IC₅₀ value of 11.0 µM, and 14, which contained an active center, -C=N⁺, exhibited antibacterial activity. An analysis of the relationship between the structures, enzyme inhibitory activity and cytotoxicity of 1–14 revealed that the substituents at C-7 of the isoquinoline nucleus could greatly affect their bioactivity. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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11 pages, 1121 KiB

Open AccessArticle

New Tripeptide Derivatives Asterripeptides A–C from Vietnamese Mangrove-Derived Fungus Aspergillus terreus LM.5.2

by Elena V. Girich, Anton B. Rasin, Roman S. Popov, Ekaterina A. Yurchenko, Ekaterina A. Chingizova, Phan Thi Hoai Trinh, Ngo Thi Duy Ngoc, Mikhail V. Pivkin, Olesya I. Zhuravleva and Anton N. Yurchenko

Mar. Drugs 2022, 20(1), 77; https://doi.org/10.3390/md20010077 - 17 Jan 2022

Cited by 5 | Viewed by 2536

Abstract

Three new tripeptide derivatives asterripeptides A–C (1–3) were isolated from Vietnamese mangrove-derived fungus Aspergillus terreus LM.5.2. Structures of isolated compounds were determined by a combination of NMR and ESIMS techniques. The absolute configurations of all stereocenters were determined using [...] Read more.

Three new tripeptide derivatives asterripeptides A–C (1–3) were isolated from Vietnamese mangrove-derived fungus Aspergillus terreus LM.5.2. Structures of isolated compounds were determined by a combination of NMR and ESIMS techniques. The absolute configurations of all stereocenters were determined using the Murfey’s method. The isolated compounds 1–3 contain a rare fungi cinnamic acid residue. The cytotoxicity of isolated compounds against several cancer cell lines and inhibition ability of sortase A from Staphylococcus aureus of asterripeptides A–C were investigated. Full article

(This article belongs to the Special Issue Marine Compounds from the Far Eastern Organisms)

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23 pages, 6786 KiB

Open AccessArticle

FGFC1 Exhibits Anti-Cancer Activity via Inhibiting NF-κB Signaling Pathway in EGFR-Mutant NSCLC Cells

by Jingwen Feng, Songlin Li, Bing Zhang, Namin Duan, Rui Zhou, Shike Yan, Jeevithan Elango, Ning Liu and Wenhui Wu

Mar. Drugs 2022, 20(1), 76; https://doi.org/10.3390/md20010076 - 17 Jan 2022

Cited by 7 | Viewed by 2837

Abstract

FGFC1, an active compound isolated from the culture of marine fungi Stachybotrys longispora FG216, elicits fibrinolytic, anti-oxidative, and anti-inflammatory activity. We have previously reported that FGFC1 inhibited the proliferation, migration, and invasion of the non-small cell lung cancer (NSCLC) cells in vitro. However, [...] Read more.

FGFC1, an active compound isolated from the culture of marine fungi Stachybotrys longispora FG216, elicits fibrinolytic, anti-oxidative, and anti-inflammatory activity. We have previously reported that FGFC1 inhibited the proliferation, migration, and invasion of the non-small cell lung cancer (NSCLC) cells in vitro. However, the precise mechanisms of FGFC1 on NSCLC and its anti-cancer activity in vivo remains unclear. Hence, this study was focused to investigate the effects and regulatory mechanisms of FGFC1 on two NSCLC cell lines, EGFR-mutant PC9 (ex19del) and EGFR wild-type H1299. Results suggested that FGFC1 significantly inhibited proliferation, colony formation, as well as triggered G0/G1 arrest and apoptosis of PC9 cells in a dose- and time-dependent manner, but no obvious inhibitory effects were observed in H1299 cells. Subsequently, transcriptome analysis revealed that FGFC1 significantly down-regulated 28 genes related to the NF-κB pathway, including IL-6, TNF-α, and ICAM-1 in the PC9 cells. We further confirmed that FGFC1 decreased the expression of protein p-IKKα/β, p-p65, p-IκB, IL-6, and TNF-α. Moreover, NF-κB inhibitor PDTC could strengthen the effects of FGFC1 on the expression of CDK4, Cyclin D1, cleaved-PARP-1, and cleaved-caspase-3 proteins, suggesting that the NF-κB pathway plays a major role in FGFC1-induced cell cycle arrest and apoptosis. Correspondingly, the nuclear translocation of p-p65 was also suppressed by FGFC1 in PC9 cells. Finally, the intraperitoneal injection of FGFC1 remarkably inhibited PC9 xenograft growth and decreased the expression of Ki-67, p-p65, IL-6, and TNF-α in tumors. Our results indicated that FGFC1 exerted anti-cancer activity in PC9 cells via inhibiting the NF-κB signaling pathway, providing a possibility for FGFC1 to be used as a lead compound for the treatment of NSCLC in the future. Full article

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26 pages, 5696 KiB

Open AccessReview

Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents

by Elisabete Lima and Jorge Medeiros

Mar. Drugs 2022, 20(1), 75; https://doi.org/10.3390/md20010075 - 15 Jan 2022

Cited by 10 | Viewed by 3290

Abstract

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, [...] Read more.

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by β-amyloid (Aβ) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated τ-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization. Full article

(This article belongs to the Special Issue Anti-Alzheimer Agents from Marine Sources)

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20 pages, 5174 KiB

Open AccessArticle

Actinoporin-like Proteins Are Widely Distributed in the Phylum Porifera

by Kenneth Sandoval and Grace P. McCormack

Mar. Drugs 2022, 20(1), 74; https://doi.org/10.3390/md20010074 - 15 Jan 2022

Cited by 3 | Viewed by 2949

Abstract

Actinoporins are proteinaceous toxins known for their ability to bind to and create pores in cellular membranes. This quality has generated interest in their potential use as new tools, such as therapeutic immunotoxins. Isolated historically from sea anemones, genes encoding for similar actinoporin-like [...] Read more.

Actinoporins are proteinaceous toxins known for their ability to bind to and create pores in cellular membranes. This quality has generated interest in their potential use as new tools, such as therapeutic immunotoxins. Isolated historically from sea anemones, genes encoding for similar actinoporin-like proteins have since been found in a small number of other animal phyla. Sequencing and de novo assembly of Irish Haliclona transcriptomes indicated that sponges also possess similar genes. An exhaustive analysis of publicly available sequencing data from other sponges showed that this is a potentially widespread feature of the Porifera. While many sponge proteins possess a sequence similarity of 27.70–59.06% to actinoporins, they show consistency in predicted structure. One gene copy from H. indistincta has significant sequence similarity to sea anemone actinoporins and possesses conserved residues associated with the fundamental roles of sphingomyelin recognition, membrane attachment, oligomerization, and pore formation, indicating that it may be an actinoporin. Phylogenetic analyses indicate frequent gene duplication, no distinct clade for sponge-derived proteins, and a stronger signal towards actinoporins than similar proteins from other phyla. Overall, this study provides evidence that a diverse array of Porifera represents a novel source of actinoporin-like proteins which may have biotechnological and pharmaceutical applications. Full article

(This article belongs to the Special Issue Marine Sponge Biotechnology)

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10 pages, 2113 KiB

Open AccessArticle

Isolation and Characterization of a Yellow Xanthophyll Pigment-Producing Marine Bacterium, Erythrobacter sp. SDW2 Strain, in Coastal Seawater

by Sun Wook Jeong, Jung Eun Yang and Yong Jun Choi

Mar. Drugs 2022, 20(1), 73; https://doi.org/10.3390/md20010073 - 14 Jan 2022

Cited by 10 | Viewed by 2512

Abstract

Xanthophylls, a yellow pigment belonging to the carotenoid family, have attracted much attention for industrial applications due to their versatile nature. We report the isolation of a homo xanthophyll pigment-producing marine bacterium, identified as the Erythrobacter sp. SDW2 strain, from coastal seawater. The [...] Read more.

Xanthophylls, a yellow pigment belonging to the carotenoid family, have attracted much attention for industrial applications due to their versatile nature. We report the isolation of a homo xanthophyll pigment-producing marine bacterium, identified as the Erythrobacter sp. SDW2 strain, from coastal seawater. The isolated Erythrobacter sp. SDW2 strain can produce 263 ± 12.9 mg/L (89.7 ± 5.4 mg/g dry cell weight) of yellow xanthophyll pigment from 5 g/L of glucose. Moreover, the xanthophyll pigment produced by the SDW2 strain exhibits remarkable antioxidative activities, confirmed by the DPPH (73.4 ± 1.4%) and ABTS (84.9 ± 0.7%) assays. These results suggest that the yellow xanthophyll pigment-producing Erythrobacter sp. SDW2 strain could be a promising industrial microorganism for producing marine-derived bioactive compounds with potential for foods, cosmetics, and pharmaceuticals. Full article

(This article belongs to the Special Issue Marine Pigments)

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15 pages, 2461 KiB

Open AccessArticle

New Deoxyenhygrolides from Plesiocystis pacifica Provide Insights into Butenolide Core Biosynthesis

by Joachim J. Hug, Louise Kjaerulff, Ronald Garcia and Rolf Müller

Mar. Drugs 2022, 20(1), 72; https://doi.org/10.3390/md20010072 - 14 Jan 2022

Cited by 8 | Viewed by 2043

Abstract

Marine myxobacteria present a virtually unexploited reservoir for the discovery of natural products with diverse biological functions and novel chemical scaffolds. We report here the isolation and structure elucidation of eight new deoxyenhygrolides (1–8) from the marine myxobacterium Plesiocystis [...] Read more.

Marine myxobacteria present a virtually unexploited reservoir for the discovery of natural products with diverse biological functions and novel chemical scaffolds. We report here the isolation and structure elucidation of eight new deoxyenhygrolides (1–8) from the marine myxobacterium Plesiocystis pacifica DSM 14875^T. The herein described deoxyenhygrolides C–J (1–8) feature a butenolide core with an ethyl residue at C-3 of the γ-lactone in contrast to the previously described derivatives, deoxyenhygrolides A and B, which feature an isobutyl residue at this position. The butenolide core is 2,4-substituted with a benzyl (1, 2 and 7), benzoyl (3 and 4) or benzyl alcohol (5, 6 and 8) moiety in the 2-position and a benzylidene (1–6) or benzylic hemiketal (7 and 8) in the 4-position. The description of these new deoxyenhygrolide derivatives, alongside genomic in silico investigation regarding putative biosynthetic genes, provides some new puzzle pieces on how this natural product class might be formed by marine myxobacteria. Full article

(This article belongs to the Special Issue Future Directions of Marine Bacterial Natural Products)

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12 pages, 1693 KiB

Open AccessArticle

Chevalones H–M: Six New α-Pyrone Meroterpenoids from the Gorgonian Coral-Derived Fungus Aspergillus hiratsukae SCSIO 7S2001

by Xia-Yu Chen, Qi Zeng, Yu-Chan Chen, Wei-Mao Zhong, Yao Xiang, Jun-Feng Wang, Xue-Feng Shi, Wei-Min Zhang, Si Zhang and Fa-Zuo Wang

Mar. Drugs 2022, 20(1), 71; https://doi.org/10.3390/md20010071 - 14 Jan 2022

Cited by 5 | Viewed by 2032

Abstract

Six new α-pyrone meroterpenoid chevalones H–M (1–6), together with six known compounds (7–12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, [...] Read more.

Six new α-pyrone meroterpenoid chevalones H–M (1–6), together with six known compounds (7–12), were isolated from the gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001 collected from Mischief Reef in the South China Sea. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and X-ray diffraction data. Compounds 1–5 and 7 showed different degrees of antibacterial activity with MIC values of 6.25–100 μg/mL. Compound 8 exhibited potent cytotoxicity against SF-268, MCF-7, and A549 cell lines with IC₅₀ values of 12.75, 9.29, and 20.11 μM, respectively. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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13 pages, 1240 KiB

Open AccessArticle

Lipid Indexes and Quality Evaluation of Omega-3 Rich Oil from the Waste of Japanese Spanish Mackerel Extracted by Supercritical CO₂

by Vikash Chandra Roy, Jin-Seok Park, Truc Cong Ho and Byung-Soo Chun

Mar. Drugs 2022, 20(1), 70; https://doi.org/10.3390/md20010070 - 13 Jan 2022

Cited by 16 | Viewed by 2727

Abstract

Japanese Spanish mackerel (JSM) (Scomberomorus niphonius) is a marine fish species containing health-beneficial polyunsaturated fatty acids (PUFAs). In the present study, the quality of JSM by-products oils extracted by supercritical CO₂ (SC-CO₂) and organic solvent extraction was compared [...] Read more.

Japanese Spanish mackerel (JSM) (Scomberomorus niphonius) is a marine fish species containing health-beneficial polyunsaturated fatty acids (PUFAs). In the present study, the quality of JSM by-products oils extracted by supercritical CO₂ (SC-CO₂) and organic solvent extraction was compared in terms of physico-chemical properties of the oils. Eicosapentaenoic acid (EPA) is one of the important polyunsaturated fatty acids present in SC-CO₂-extracted skin and muscle oil 5.81 ± 0.69% and 4.93 ± 0.06%, respectively. The amount of docosahexaenoic acid (DHA) in SC-CO₂-extracted skin and muscle oil was 12.56 ± 0.38% and 15.01 ± 0.28%, respectively. EPA and DHA are considered as important PUFAs for the development of brain function and the prevention of coronary heart diseases. Extracted oils showed considerable antioxidant activity. In the obtained oils, atherogenic index (AI) values varied from 0.72 to 0.93 and thrombogenic index (TI) ranged from 0.75 to 0.92, which is considered an acceptable level. Fatty acid composition, bio potentiality, thermogravimetric, and vitamin D analysis showed that oils extracted from JSM by-products can be a good source of oil for application in food, pharmaceutical and cosmetic industries. Therefore, the present research revealed the potentiality of green valorisation of S. niphonius by-products as a possible sustainable approach for targeting the era of zero waste. Full article

(This article belongs to the Special Issue Fishery Discards, Processing Waste and Marine By-Products Valorization in the Era of Zero Waste: From Discovery to Profit 2.0)

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19 pages, 18734 KiB

Open AccessReview

The Microstructure, Antibacterial and Antitumor Activities of Chitosan Oligosaccharides and Derivatives

by Dawei Yu, Jiayao Feng, Huimin You, Shipeng Zhou, Yan Bai, Jincan He, Hua Cao, Qishi Che, Jiao Guo and Zhengquan Su

Mar. Drugs 2022, 20(1), 69; https://doi.org/10.3390/md20010069 - 13 Jan 2022

Cited by 50 | Viewed by 4446

Abstract

Chitosan obtained from abundant marine resources has been proven to have a variety of biological activities. However, due to its poor water solubility, chitosan application is limited, and the degradation products of chitosan oligosaccharides are better than chitosan regarding performance. Chitosan oligosaccharides have [...] Read more.

Chitosan obtained from abundant marine resources has been proven to have a variety of biological activities. However, due to its poor water solubility, chitosan application is limited, and the degradation products of chitosan oligosaccharides are better than chitosan regarding performance. Chitosan oligosaccharides have two kinds of active groups, amino and hydroxyl groups, which can form a variety of derivatives, and the properties of these derivatives can be further improved. In this review, the key structures of chitosan oligosaccharides and recent studies on chitosan oligosaccharide derivatives, including their synthesis methods, are described. Finally, the antimicrobial and antitumor applications of chitosan oligosaccharides and their derivatives are discussed. Full article

(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides 2.0)

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15 pages, 2081 KiB

Open AccessArticle

Crypthecodinium cohnii Growth and Omega Fatty Acid Production in Mediums Supplemented with Extract from Recycled Biomass

by Elina Didrihsone, Konstantins Dubencovs, Mara Grube, Karlis Shvirksts, Anastasija Suleiko, Arturs Suleiko and Juris Vanags

Mar. Drugs 2022, 20(1), 68; https://doi.org/10.3390/md20010068 - 12 Jan 2022

Cited by 7 | Viewed by 2860

Abstract

Crypthecodinium cohnii is a marine heterotrophic dinoflagellate that can accumulate high amounts of omega-3 polyunsaturated fatty acids (PUFAs), and thus has the potential to replace conventional PUFAs production with eco-friendlier technology. So far, C. cohnii cultivation has been mainly carried out with the [...] Read more.

Crypthecodinium cohnii is a marine heterotrophic dinoflagellate that can accumulate high amounts of omega-3 polyunsaturated fatty acids (PUFAs), and thus has the potential to replace conventional PUFAs production with eco-friendlier technology. So far, C. cohnii cultivation has been mainly carried out with the use of yeast extract (YE) as a nitrogen source. In the present study, alternative carbon and nitrogen sources were studied: the extraction ethanol (EE), remaining after lipid extraction, as a carbon source, and dinoflagellate extract (DE) from recycled algae biomass C. cohnii as a source of carbon, nitrogen, and vitamins. In mediums with glucose and DE, the highest specific biomass growth rate reached a maximum of 1.012 h⁻¹, while the biomass yield from substrate reached 0.601 g·g⁻¹. EE as the carbon source, in comparison to pure ethanol, showed good results in terms of stimulating the biomass growth rate (an 18.5% increase in specific biomass growth rate was observed). DE supplement to the EE-based mediums promoted both the biomass growth (the specific growth rate reached 0.701 h⁻¹) and yield from the substrate (0.234 g·g⁻¹). The FTIR spectroscopy data showed that mediums supplemented with EE or DE promoted the accumulation of PUFAs/docosahexaenoic acid (DHA), when compared to mediums containing glucose and commercial YE. Full article

(This article belongs to the Special Issue Lipids in the Ocean 2021)

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18 pages, 4636 KiB

Open AccessReview

Secondary Metabolites from Marine-Derived Fungi and Actinobacteria as Potential Sources of Novel Colorectal Cancer Drugs

by Elin Julianti, Ikram Ammar Abrian, Marlia Singgih Wibowo, Muhammad Azhari, Nadya Tsurayya, Fauzia Izzati, Ario Betha Juanssilfero, Asep Bayu, Siti Irma Rahmawati and Masteria Yunovilsa Putra

Mar. Drugs 2022, 20(1), 67; https://doi.org/10.3390/md20010067 - 12 Jan 2022

Cited by 17 | Viewed by 4295

Abstract

Colorectal cancer is one of the most common cancers diagnosed in the world. Chemotheraphy is one of the most common methods used for the pharmacological treatment of this cancer patients. Nevertheless, the adverse effect of chemotherapy is not optimized for improving the quality [...] Read more.

Colorectal cancer is one of the most common cancers diagnosed in the world. Chemotheraphy is one of the most common methods used for the pharmacological treatment of this cancer patients. Nevertheless, the adverse effect of chemotherapy is not optimized for improving the quality of life of people who are older, who are the most vulnerable subpopulation. This review presents recent updates regarding secondary metabolites derived from marine fungi and actinobacteria as novel alternatives for cytotoxic agents against colorectal cancer cell lines HCT116, HT29, HCT15, RKO, Caco-2, and SW480. The observed marine-derived fungi were from the species Aspergillus sp., Penicillium sp., Neosartorya sp., Dichotomomyces sp., Paradendryphiella sp., and Westerdykella sp. Additionally, Streptomyces sp. and Nocardiopsis sp. are actinobacteria discussed in this study. Seventy one compounds reviewed in this study were grouped on the basis of their chemical structures. Indole alkaloids and diketopiperazines made up most compounds with higher potencies when compared with other groups. The potency of indole alkaloids and diketopiperazines was most probably due to halogen-based functional groups and sulfide groups, respectively. Full article

(This article belongs to the Special Issue Development and Application of Marine-Sourced Anti-Cancer and Cancer Pain Control Agents II)

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16 pages, 7760 KiB

Open AccessArticle

Cloning and Characterization of a Novel Alginate Lyase from Paenibacillus sp. LJ-23

by Mingpeng Wang, Lei Chen, Zhengyu Lou, Xueting Yuan, Guiping Pan, Xiaoyan Ren and Pengyu Wang

Mar. Drugs 2022, 20(1), 66; https://doi.org/10.3390/md20010066 - 12 Jan 2022

Cited by 7 | Viewed by 1995

Abstract

As a low molecular weight alginate, alginate oligosaccharides (AOS) exhibit improved water solubility, better bioavailability, and comprehensive health benefits. In addition, their biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and gelling capability make them an excellent biomaterial with a dual curative effect when applied in a [...] Read more.

As a low molecular weight alginate, alginate oligosaccharides (AOS) exhibit improved water solubility, better bioavailability, and comprehensive health benefits. In addition, their biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and gelling capability make them an excellent biomaterial with a dual curative effect when applied in a drug delivery system. In this paper, a novel alginate lyase, Algpt, was cloned and characterized from a marine bacterium, Paenibacillus sp. LJ-23. The purified enzyme was composed of 387 amino acid residues, and had a molecular weight of 42.8 kDa. The optimal pH of Algpt was 7.0 and the optimal temperature was 45 °C. The analysis of the conserved domain and the prediction of the three-dimensional structure indicated that Algpt was a novel alginate lyase. The dominant degradation products of Algpt on alginate were AOS dimer to octamer, depending on the incubation time, which demonstrated that Algpt degraded alginate in an endolytic manner. In addition, Algpt was a salt-independent and thermo-tolerant alginate lyase. Its high stability and wide adaptability endow Algpt with great application potential for the efficient preparation of AOS with different sizes and AOS-based products. Full article

(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)

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13 pages, 2867 KiB

Open AccessArticle

Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis

by Marcello Casertano, Massimo Genovese, Paolo Paoli, Alice Santi, Anna Aiello, Marialuisa Menna and Concetta Imperatore

Mar. Drugs 2022, 20(1), 65; https://doi.org/10.3390/md20010065 - 11 Jan 2022

Cited by 7 | Viewed by 2002

Abstract

The chemical investigation of the Mediterranean ascidian Clavelina lepadiformis has led to the isolation of a new lepadin, named lepadin L, and two known metabolites belonging to the same family, lepadins A and B. The planar structure and relative configuration of the decahydroquinoline [...] Read more.

The chemical investigation of the Mediterranean ascidian Clavelina lepadiformis has led to the isolation of a new lepadin, named lepadin L, and two known metabolites belonging to the same family, lepadins A and B. The planar structure and relative configuration of the decahydroquinoline ring of lepadin L were established both by means of HR-ESIMS and by a detailed as extensive analysis of 1D and 2D NMR spectra. Moreover, microscale derivatization of the new alkaloid lepadin L was performed to assess the relative configuration of the functionalized alkyl side chain. Lepadins A, B, and L were tested for their cytotoxic activity on a panel of cancer cell lines (human melanoma [A375], human breast [MDA-MB-468], human colon adenocarcinoma [HT29], human colorectal carcinoma [HCT116], and mouse myoblast [C2C12]). Interestingly, a deeper investigation into the mechanism of action of the most cytotoxic metabolite, lepadin A, on the A375 cells has highlighted its ability to induce a strongly inhibition of cell migration, G2/M phase cell cycle arrest and a dose-dependent decrease of cell clonogenity, suggesting that it is able to impair self-renewing capacity of A375 cells. Full article

(This article belongs to the Special Issue Search for New Drug Candidates and Their Lead Compounds from Tunicates)

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14 pages, 2155 KiB

Open AccessArticle

Variations in the Composition, Antioxidant and Antimicrobial Activities of Cystoseira compressa during Seasonal Growth

by Martina Čagalj, Danijela Skroza, María del Carmen Razola-Díaz, Vito Verardo, Daniela Bassi, Roberta Frleta, Ivana Generalić Mekinić, Giulia Tabanelli and Vida Šimat

Mar. Drugs 2022, 20(1), 64; https://doi.org/10.3390/md20010064 - 11 Jan 2022

Cited by 29 | Viewed by 3067

Abstract

The underexplored biodiversity of seaweeds has recently drawn great attention from researchers to find the bioactive compounds that might contribute to the growth of the blue economy. In this study, we aimed to explore the effect of seasonal growth (from May to September) [...] Read more.

The underexplored biodiversity of seaweeds has recently drawn great attention from researchers to find the bioactive compounds that might contribute to the growth of the blue economy. In this study, we aimed to explore the effect of seasonal growth (from May to September) on the in vitro antioxidant (FRAP, DPPH, and ORAC) and antimicrobial effects (MIC and MBC) of Cystoseira compressa collected in the Central Adriatic Sea. Algal compounds were analyzed by UPLC-PDA-ESI-QTOF, and TPC and TTC were determined. Fatty acids, among which oleic acid, palmitoleic acid, and palmitic acid were the dominant compounds in samples. The highest TPC, TTC and FRAP were obtained for June extract, 83.4 ± 4.0 mg GAE/g, 8.8 ± 0.8 mg CE/g and 2.7 ± 0.1 mM TE, respectively. The highest ORAC value of 72.1 ± 1.2 µM TE was obtained for the August samples, and all samples showed extremely high free radical scavenging activity and DPPH inhibition (>80%). The MIC and MBC results showed the best antibacterial activity for the June, July and August samples, when sea temperature was the highest, against Listeria monocytogenes, Staphylococcus aureus, and Salmonella enteritidis. The results show C. compressa as a potential species for the industrial production of nutraceuticals or functional food ingredients. Full article

(This article belongs to the Special Issue Novel Applications and Technologies for the Industrial Exploitation of Algal Derived Marine Bioactives as Nutraceuticals or Pharmaceuticals)

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23 pages, 7031 KiB

Open AccessArticle

Anticancer Effects of New Ceramides Isolated from the Red Sea Red Algae Hypnea musciformis in a Model of Ehrlich Ascites Carcinoma: LC-HRMS Analysis Profile and Molecular Modeling

by Sameh S. Elhady, Eman S. Habib, Reda F. A. Abdelhameed, Marwa S. Goda, Reem M. Hazem, Eman T. Mehanna, Mohamed A. Helal, Khaled M. Hosny, Reem M. Diri, Hashim A. Hassanean, Amany K. Ibrahim, Enas E. Eltamany, Usama Ramadan Abdelmohsen and Safwat A. Ahmed

Mar. Drugs 2022, 20(1), 63; https://doi.org/10.3390/md20010063 - 10 Jan 2022

Cited by 11 | Viewed by 2643

Abstract

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids—docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid [...] Read more.

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids—docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6—as well as three ceramides—A (1), B (2), and C (3)—with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea musciformis in an experimental model of EAC. Full article

(This article belongs to the Special Issue Novel Applications and Technologies for the Industrial Exploitation of Algal Derived Marine Bioactives as Nutraceuticals or Pharmaceuticals)

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28 pages, 2567 KiB

Open AccessReview

Extremophilic Fungi from Marine Environments: Underexplored Sources of Antitumor, Anti-Infective and Other Biologically Active Agents

by Lesley-Ann Giddings and David J. Newman

Mar. Drugs 2022, 20(1), 62; https://doi.org/10.3390/md20010062 - 10 Jan 2022

Cited by 17 | Viewed by 4105

Abstract

Marine environments are underexplored terrains containing fungi that produce a diversity of natural products given unique environmental pressures and nutrients. While bacteria are commonly the most studied microorganism for natural products in the marine world, marine fungi are also abundant but remain an [...] Read more.

Marine environments are underexplored terrains containing fungi that produce a diversity of natural products given unique environmental pressures and nutrients. While bacteria are commonly the most studied microorganism for natural products in the marine world, marine fungi are also abundant but remain an untapped source of bioactive metabolites. Given that their terrestrial counterparts have been a source of many blockbuster antitumor agents and anti-infectives, including camptothecin, the penicillins, and cyclosporin A, marine fungi also have the potential to produce new chemical scaffolds as leads to potential drugs. Fungi are more phylogenetically diverse than bacteria and have larger genomes that contain many silent biosynthetic gene clusters involved in making bioactive compounds. However, less than 5% of all known fungi have been cultivated under standard laboratory conditions. While the number of reported natural products from marine fungi is steadily increasing, their number is still significantly lower compared to those reported from their bacterial counterparts. Herein, we discuss many varied cytotoxic and anti-infective fungal metabolites isolated from extreme marine environments, including symbiotic associations as well as extreme pressures, temperatures, salinity, and light. We also discuss cultivation strategies that can be used to produce new bioactive metabolites or increase their production. This review presents a large number of reported structures though, at times, only a few of a large number of related structures are shown. Full article

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16 pages, 3185 KiB

Open AccessReview

Marine Collagen: A Promising Biomaterial for Wound Healing, Skin Anti-Aging, and Bone Regeneration

by Sarah Geahchan, Parnian Baharlouei and Azizur Rahman

Mar. Drugs 2022, 20(1), 61; https://doi.org/10.3390/md20010061 - 10 Jan 2022

Cited by 70 | Viewed by 13224

Abstract

Marine organisms harbor numerous bioactive substances that can be utilized in the pharmaceutical and cosmetic industries. Scientific research on various applications of collagen extracted from these organisms has become increasingly prevalent. Marine collagen can be used as a biomaterial because it is water [...] Read more.

Marine organisms harbor numerous bioactive substances that can be utilized in the pharmaceutical and cosmetic industries. Scientific research on various applications of collagen extracted from these organisms has become increasingly prevalent. Marine collagen can be used as a biomaterial because it is water soluble, metabolically compatible, and highly accessible. Upon review of the literature, it is evident that marine collagen is a versatile compound capable of healing skin injuries of varying severity, as well as delaying the natural human aging process. From in vitro to in vivo experiments, collagen has demonstrated its ability to invoke keratinocyte and fibroblast migration as well as vascularization of the skin. Additionally, marine collagen and derivatives have proven beneficial and useful for both osteoporosis and osteoarthritis prevention and treatment. Other bone-related diseases may also be targeted by collagen, as it is capable of increasing bone mineral density, mineral deposition, and importantly, osteoblast maturation and proliferation. In this review, we demonstrate the advantages of marine collagen over land animal sources and the biomedical applications of marine collagen related to bone and skin damage. Finally, some limitations of marine collagen are briefly discussed. Full article

(This article belongs to the Special Issue Marine Skeletal Biopolymers and Proteins 2)

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17 pages, 2676 KiB

Open AccessArticle

Influence of the Structural Features of Carrageenans from Red Algae of the Far Eastern Seas on Their Antiviral Properties

by Natalia V. Krylova, Anna O. Kravchenko, Olga V. Iunikhina, Anastasia B. Pott, Galina N. Likhatskaya, Aleksandra V. Volod’ko, Tatyana S. Zaporozhets, Mikhail Y. Shchelkanov and Irina M. Yermak

Mar. Drugs 2022, 20(1), 60; https://doi.org/10.3390/md20010060 - 08 Jan 2022

Cited by 12 | Viewed by 2381

Abstract

The structural diversity and unique physicochemical properties of sulphated polysaccharides of red algae carrageenans (CRGs), to a great extent, determine the wide range of their antiviral properties. This work aimed to compare the antiviral activities of different structural types of CRGs: against herpes [...] Read more.

The structural diversity and unique physicochemical properties of sulphated polysaccharides of red algae carrageenans (CRGs), to a great extent, determine the wide range of their antiviral properties. This work aimed to compare the antiviral activities of different structural types of CRGs: against herpes simplex virus type 1 (HSV-1) and enterovirus (ECHO-1). We found that CRGs significantly increased the resistance of Vero cells to virus infection (preventive effect), directly affected virus particles (virucidal effect), inhibited the attachment and penetration of virus to cells, and were more effective against HSV-1. CRG1 showed the highest virucidal effect on HSV-1 particles with a selective index (SI) of 100. CRG2 exhibited the highest antiviral activity by inhibiting HSV-1 and ECHO-1 plaque formation, with a SI of 110 and 59, respectively, when it was added before virus infection. CRG2 also significantly reduced the attachment of HSV-1 and ECHO-1 to cells compared to other CRGs. It was shown by molecular docking that tetrasaccharides—CRGs are able to bind with the HSV-1 surface glycoprotein, gD, to prevent virus–cell interactions. The revealed differences in the effect of CRGs on different stages of the lifecycle of the viruses are apparently related to the structural features of the investigated compounds. Full article

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14 pages, 1916 KiB

Open AccessArticle

Sonneradon A Extends Lifespan of Caenorhabditis elegans by Modulating Mitochondrial and IIS Signaling Pathways

by Shu Jiang, Cui-Ping Jiang, Pei Cao, Yong-Hong Liu, Cheng-Hai Gao and Xiang-Xi Yi

Mar. Drugs 2022, 20(1), 59; https://doi.org/10.3390/md20010059 - 08 Jan 2022

Cited by 6 | Viewed by 2297

Abstract

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Sonneradon A (SDA), a new compound first extracted from the edible fruits of mangrove Sonneratia apetala, showed remarkable antiaging activity. However, the role of SDA [...] Read more.

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Sonneradon A (SDA), a new compound first extracted from the edible fruits of mangrove Sonneratia apetala, showed remarkable antiaging activity. However, the role of SDA in antiaging remains unclear. In this article, we studied the function of SDA in antiaging by using the animal model Caenorhabditis elegans. Results showed that SDA inhibited production of reactive oxygen species (ROS) by 53%, and reduced the accumulation of aging markers such as lipids and lipofuscins. Moreover, SDA also enhanced the innate immune response to Pseudomonas aeruginosa infection. Genetic analysis of a series of mutants showed that SDA extended the lifespan of the mutants of eat-2 and glp-1. Together, this effect may be related to the enhanced resistance to oxidative stress via mitochondrial and insulin/insulin-like growth factor-1 signaling (IIS) pathways. The results of this study provided new evidence for an antiaging effect of SDA in C. elegans, as well as insights into the implication of antiaging activity of SDA in higher organisms. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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36 pages, 5377 KiB

Open AccessFeature PaperReview

Bioactive Marine Xanthones: A Review

by José X. Soares, Daniela R. P. Loureiro, Ana Laura Dias, Salete Reis, Madalena M. M. Pinto and Carlos M. M. Afonso

Mar. Drugs 2022, 20(1), 58; https://doi.org/10.3390/md20010058 - 08 Jan 2022

Cited by 21 | Viewed by 2941

Abstract

The marine environment is an important source of specialized metabolites with valuable biological activities. Xanthones are a relevant chemical class of specialized metabolites found in this environment due to their structural variety and their biological activities. In this work, a comprehensive literature review [...] Read more.

The marine environment is an important source of specialized metabolites with valuable biological activities. Xanthones are a relevant chemical class of specialized metabolites found in this environment due to their structural variety and their biological activities. In this work, a comprehensive literature review of marine xanthones reported up to now was performed. A large number of bioactive xanthone derivatives (169) were identified, and their structures, biological activities, and natural sources were described. To characterize the chemical space occupied by marine-derived xanthones, molecular descriptors were calculated. For the analysis of the molecular descriptors, the xanthone derivatives were grouped into five structural categories (simple, prenylated, O-heterocyclic, complex, and hydroxanthones) and six biological activities (antitumor, antibacterial, antidiabetic, antifungal, antiviral, and miscellaneous). Moreover, the natural product-likeness and the drug-likeness of marine xanthones were also assessed. Marine xanthone derivatives are rewarding bioactive compounds and constitute a promising starting point for the design of other novel bioactive molecules. Full article

(This article belongs to the Special Issue Marine Benzophenones and Xanthones: Isolation and Synthesis)

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18 pages, 1883 KiB

Open AccessArticle

Bioprospecting of Less-Polar Fractions of Ericaria crinita and Ericaria amentacea: Developmental Toxicity and Antioxidant Activity

by Sanja Radman, Lara Čižmek, Sanja Babić, Ana-Marija Cikoš, Rozelindra Čož-Rakovac, Stela Jokić and Igor Jerković

Mar. Drugs 2022, 20(1), 57; https://doi.org/10.3390/md20010057 - 06 Jan 2022

Cited by 20 | Viewed by 2587

Abstract

Ericaria crinita and Ericaria amentacea from the Adriatic Sea (Croatia) were investigated with respect to the presence of less-polar compounds for the first time after fractionation by solid-phase extraction (SPE). The composition of less-polar fractions of freeze-dried E. crinita (FdEc) and E. amentacea [...] Read more.

Ericaria crinita and Ericaria amentacea from the Adriatic Sea (Croatia) were investigated with respect to the presence of less-polar compounds for the first time after fractionation by solid-phase extraction (SPE). The composition of less-polar fractions of freeze-dried E. crinita (FdEc) and E. amentacea (FdEa) were analyzed by high-performance liquid chromatography–high-resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). The major identified compounds were: amides of higher aliphatic acids (palmitoleamide, linoleamide, palmitamide, oleamide and erucamide) and related compounds, carotenoid (fucoxanthin), chlorophyll derivatives (pheophytin a and b and their derivatives) and higher terpenes (loliolide, isoamijiol with its oxidation product), β-stigmasterol and (3β,6α)-14-methylergosta-8,24(28)-diene-3,6-diol). The toxic effects observed on the less-polar fractions obtained from Ericaria species on zebrafish Danio rerio embryos could be associated with the high abundance of all five detected amides. The antioxidant activity of the fractions was evaluated by means of five independent assays, including the reduction of the radical cation (ABTS), the oxygen radical absorbance capacity (ORAC), ferric-reducing antioxidant power (FRAP), the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay and the Folin–Ciocalteu method. A higher antioxidant activity of E. amentacea in comparison to that of the E. crinita fractions was found with IC₅₀ concentrations of 0.072 and 1.177 mg/mL, respectively. The correlation between the activity and the chemical composition revealed that the synergistic effect of different compounds impacted their antioxidant response. Full article

(This article belongs to the Special Issue Seaweed Bioactive Metabolites: Health Benefits and Potential Applications)

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21 pages, 18783 KiB

Open AccessArticle

Green Synthesis of Silver Nanoparticles by the Cyanobacteria Synechocystis sp.: Characterization, Antimicrobial and Diabetic Wound-Healing Actions

by Nancy S. Younis, Maged E. Mohamed and Nermin A. El Semary

Mar. Drugs 2022, 20(1), 56; https://doi.org/10.3390/md20010056 - 06 Jan 2022

Cited by 29 | Viewed by 3459

Abstract

Green nanotechnology is now accepted as an environmentally friendly and cost-effective advance with various biomedical applications. The cyanobacterium Synechocystis sp. is a unicellular spherical cyanobacterium with photo- and hetero-trophic capabilities. This study investigates the ability of this cyanobacterial species to produce silver nanoparticles [...] Read more.

Green nanotechnology is now accepted as an environmentally friendly and cost-effective advance with various biomedical applications. The cyanobacterium Synechocystis sp. is a unicellular spherical cyanobacterium with photo- and hetero-trophic capabilities. This study investigates the ability of this cyanobacterial species to produce silver nanoparticles (AgNPs) and the wound-healing properties of the produced nanoparticles in diabetic animals. Methods: UV–visible and FT-IR spectroscopy and and electron microscopy techniques investigated AgNPs’ producibility by Synechocystis sp. when supplemented with silver ion source. The produced AgNPs were evaluated for their antimicrobial, anti-oxidative, anti-inflammatory, and diabetic wound healing along with their angiogenesis potential. Results: The cyanobacterium biosynthesized spherical AgNPs with a diameter range of 10 to 35 nm. The produced AgNPs exhibited wound-healing properties verified with increased contraction percentage, tensile strength and hydroxyproline level in incision diabetic wounded animals. AgNPs treatment decreased epithelialization period, amplified the wound closure percentage, and elevated collagen, hydroxyproline and hexosamine contents, which improved angiogenesis factors’ contents (HIF-1α, TGF-β1 and VEGF) in excision wound models. AgNPs intensified catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities, and glutathione (GSH) and nitric oxide content and reduced malondialdehyde (MDA) level. IL-1β, IL-6, TNF-α, and NF-κB (the inflammatory mediators) were decreased with AgNPs’ topical application. Conclusion: Biosynthesized AgNPs via Synechocystis sp. exhibited antimicrobial, anti-oxidative, anti-inflammatory, and angiogenesis promoting effects in diabetic wounded animals. Full article

(This article belongs to the Special Issue Bioactive Products from Marine Cyanobacteria and Their Potential Therapeutic Applications)

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9 pages, 1326 KiB

Open AccessArticle

A Promising Potential of Brown Algae Sargassum polycystum as Irreversible Hydrocolloid Impression Material

by Nurlindah Hamrun, Bahruddin Talib, Muhammad Ruslin, Hasminar Pangeran, Mochammad Hatta, Erni Marlina, Andi Sitti Hajrah Yusuf, Takashi Saito and Keng-Liang Ou

Mar. Drugs 2022, 20(1), 55; https://doi.org/10.3390/md20010055 - 06 Jan 2022

Cited by 4 | Viewed by 2277

Abstract

This study aimed to investigate the potential use of brown algae Sargassum polycystum as irreversible hydrocolloid (alginate) impression material. Potassium alginate extracted from Sargassum polycystum was prepared in three different compositions (14%, 15%, and 16%) and mixed with other standard components to form [...] Read more.

This study aimed to investigate the potential use of brown algae Sargassum polycystum as irreversible hydrocolloid (alginate) impression material. Potassium alginate extracted from Sargassum polycystum was prepared in three different compositions (14%, 15%, and 16%) and mixed with other standard components to form an alginate impression material. Prior to that, the purity of potassium alginate was quantified with Fourier Transform Infrared Spectroscopy (FTIR) analysis. As a control material, the alginate impression material from a commercially available product was used. All alginate impression materials were then applied to a die stone model. Dimensional accuracy was measured by calculating the mesiodistal width of incisors in the generated dental cast using a digital caliper 0.01 accuracy (five replications). In addition, to evaluate the dimensional stability, the impression results were poured at four different periods (immediately, 5 min, 10 min, and 15 min). An independent t-test was performed to compare the measurement results with p < 0.05 considered significant. Analytical results confirm that the impression material containing 15% potassium alginate gives the best dimensional accuracy similar to control (p > 0.05). Meanwhile, the optimal dimensional stability was produced in the impression material containing 16% potassium alginate. Our study suggested that brown algae Sargassum polycystum has a promising potential to be used as an alginate impression material in clinical application. Full article

(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)

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20 pages, 3074 KiB

Open AccessArticle

Characterization of an Insoluble and Soluble Form of Melanin Produced by Streptomyces cavourensis SV 21, a Sea Cucumber Associated Bacterium

by Joko Tri Wibowo, Matthias Y. Kellermann, Lars-Erik Petersen, Yustian R. Alfiansah, Colleen Lattyak and Peter J. Schupp

Mar. Drugs 2022, 20(1), 54; https://doi.org/10.3390/md20010054 - 06 Jan 2022

Cited by 16 | Viewed by 3127

Abstract

Melanin is a widely distributed and striking dark-colored pigment produced by countless living organisms. Although a wide range of bioactivities have been recognized, there are still major constraints in using melanin for biotechnological applications such as its fragmentary known chemical structure and its [...] Read more.

Melanin is a widely distributed and striking dark-colored pigment produced by countless living organisms. Although a wide range of bioactivities have been recognized, there are still major constraints in using melanin for biotechnological applications such as its fragmentary known chemical structure and its insolubility in inorganic and organic solvents. In this study, a bacterial culture of Streptomyces cavourensis SV 21 produced two distinct forms of melanin: (1) a particulate, insoluble form as well as (2) a rarely observed water-soluble form. The here presented novel, acid-free purification protocol of purified particulate melanin (PPM) and purified dissolved melanin (PDM) represents the basis for an in-depth comparison of their physicochemical and biological properties, which were compared to the traditional acid-based precipitation of melanin (AM) and to a synthetic melanin standard (SM). Our data show that the differences in solubility between PDM and PPM in aqueous solutions may be a result of different adjoining cation species, since the soluble PDM polymer is largely composed of Mg²⁺ ions and the insoluble PPM is dominated by Ca²⁺ ions. Furthermore, AM shared most properties with SM, which is likely attributed to a similar, acid-based production protocol. The here presented gentler approach of purifying melanin facilitates a new perspective of an intact form of soluble and insoluble melanin that is less chemical altered and thus closer to its original biological form. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Streptomyces)

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26 pages, 2521 KiB

Open AccessEditor’s ChoiceArticle

Computer-Aided Drug Design (CADD) to De-Orphanize Marine Molecules: Finding Potential Therapeutic Agents for Neurodegenerative and Cardiovascular Diseases

by Laura Llorach-Pares, Alfons Nonell-Canals, Conxita Avila and Melchor Sanchez-Martinez

Mar. Drugs 2022, 20(1), 53; https://doi.org/10.3390/md20010053 - 05 Jan 2022

Cited by 5 | Viewed by 3914

Abstract

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home [...] Read more.

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home to much of the planet’s biodiversity. Biodiversity is directly related to chemodiversity, which can inspire new drug discoveries. Therefore, natural products (NPs) in general, and MNPs in particular, have been used for decades as a source of inspiration for the design of new drugs. However, NPs present both opportunities and challenges. These difficulties can be technical, such as the need to dive or trawl to collect the organisms possessing the compounds, or biological, due to their particular marine habitats and the fact that they can be uncultivable in the laboratory. For all these difficulties, the contributions of CADD can play a very relevant role in simplifying their study, since, for example, no biological sample is needed to carry out an in-silico analysis. Therefore, the amount of natural product that needs to be used in the entire preclinical and clinical study is significantly reduced. Here, we exemplify how this combination between CADD and MNPs can help unlock their therapeutic potential. In this study, using a set of marine invertebrate molecules, we elucidate their possible molecular targets and associated therapeutic potential, establishing a pipeline that can be replicated in future studies. Full article

(This article belongs to the Special Issue Marine Drugs Research in Spain)

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11 pages, 1482 KiB

Open AccessEditor’s ChoiceArticle

Unveiling the Chemical Diversity of the Deep-Sea Sponge Characella pachastrelloides

by Sam Afoullouss, Anthony R. Sanchez, Laurence K. Jennings, Younghoon Kee, A. Louise Allcock and Olivier P. Thomas

Mar. Drugs 2022, 20(1), 52; https://doi.org/10.3390/md20010052 - 05 Jan 2022

Cited by 1 | Viewed by 4923

Abstract

Sponges are at the forefront of marine natural product research. In the deep sea, extreme conditions have driven secondary metabolite pathway evolution such that we might expect deep-sea sponges to yield a broad range of unique natural products. Here, we investigate the chemodiversity [...] Read more.

Sponges are at the forefront of marine natural product research. In the deep sea, extreme conditions have driven secondary metabolite pathway evolution such that we might expect deep-sea sponges to yield a broad range of unique natural products. Here, we investigate the chemodiversity of a deep-sea tetractinellid sponge, Characella pachastrelloides, collected from ~800 m depth in Irish waters. First, we analyzed the MS/MS data obtained from fractions of this sponge on the GNPS public online platform to guide our exploration of its chemodiversity. Novel glycolipopeptides named characellides were previously isolated from the sponge and herein cyanocobalamin, a manufactured form of vitamin B₁₂, not previously found in nature, was isolated in a large amount. We also identified several poecillastrins from the molecular network, a class of polyketide known to exhibit cytotoxicity. Light sensitivity prevented the isolation and characterization of these polyketides, but their presence was confirmed by characteristic NMR and MS signals. Finally, we isolated the new betaine 6-methylhercynine, which contains a unique methylation at C-2 of the imidazole ring. This compound showed potent cytotoxicity towards against HeLa (cervical cancer) cells. Full article

(This article belongs to the Special Issue Discovering Marine Bioactive Compounds by Molecular Networking)

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14 pages, 3644 KiB

Open AccessArticle

Mono- and Dimeric Xanthones with Anti-Glioma and Anti-Inflammatory Activities from the Ascidian-Derived Fungus Diaporthe sp. SYSU-MS4722

by Senhua Chen, Heng Guo, Minghua Jiang, Qilin Wu, Jing Li, Hongjie Shen and Lan Liu

Mar. Drugs 2022, 20(1), 51; https://doi.org/10.3390/md20010051 - 05 Jan 2022

Cited by 7 | Viewed by 1932

Abstract

Seven new xanthones, diaporthones A−G (1−7), together with 13 known analogues, including five mono- (8−14) and six dimeric xanthones (15−20), were obtained from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar [...] Read more.

Seven new xanthones, diaporthones A−G (1−7), together with 13 known analogues, including five mono- (8−14) and six dimeric xanthones (15−20), were obtained from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HR-ESIMS). The absolute configurations of 1−7 were clearly identified by X-ray crystallographic analysis and calculation of the ECD Spectra. Compounds 15−20 showed significant anti-inflammatory activity with IC₅₀ values between 6.3 and 8.0 μM. In addition, dimeric xanthones (15−20) showed selective cytotoxicity against T98G cell lines with IC₅₀ values ranging from 19.5 to 78.0 μM. Full article

(This article belongs to the Special Issue Marine Drug Research in China: Selected Papers from the 15-NASMD Conference)

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14 pages, 2762 KiB

Open AccessArticle

Antithrombotic Activity of Heparinoid G2 and Its Derivatives from the Clam Coelomactra antiquata

by Guanlan Chen, Rui Zeng, Xin Wang, Hongying Cai, Jiajia Chen, Yingxiong Zhong, Saiyi Zhong and Xuejing Jia

Mar. Drugs 2022, 20(1), 50; https://doi.org/10.3390/md20010050 - 05 Jan 2022

Cited by 5 | Viewed by 1742

Abstract

Clam heparinoid G2 (60.25 kDa) and its depolymerized derivatives DG1 (24.48 kDa) and DG2 (6.75 kDa) prepared from Coelomactra antiquata have been documented to have excellent fibrinolytic and anticoagulant activity. In this study, to further explore the antithrombotic activity of G2, DG1 and [...] Read more.

Clam heparinoid G2 (60.25 kDa) and its depolymerized derivatives DG1 (24.48 kDa) and DG2 (6.75 kDa) prepared from Coelomactra antiquata have been documented to have excellent fibrinolytic and anticoagulant activity. In this study, to further explore the antithrombotic activity of G2, DG1 and DG2, azure A, sheep plasma, and clot lytic rate assays were used to determine their anticoagulant and thrombolytic activity in vitro. The results indicated that the anticoagulant titer of G2 was approximately 70% that of heparin and the thrombolytic activity of DG2 was greater than G2, DG1, and heparin activities. Moreover, in a carrageenan-induced venous thrombosis model, oral administration of G2 and DG1 each at 20 mg/kg and 40 mg/kg for 7 days significantly reduced blacktail thrombus formation, increased tissue-type plasminogen activator, fibrin degradation products, and D-dimer levels, decreased von Willebrand factor and thromboxane B2 levels, and restored phylum and genus abundance changes of intestinal bacteria. DG2 had no antithrombotic effect. At 20 mg/kg, G2, DG1, and heparin had comparable antithrombotic activities, and DG1 at 40 mg/kg had more muscular antithrombotic activity than G2. Thus, DG1 could be an antithrombotic oral agent owing to its more robust antithrombotic activity and lower molecular weight. Full article

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11 pages, 1876 KiB

Open AccessArticle

Interactions of Nereistoxin and Its Analogs with Vertebrate Nicotinic Acetylcholine Receptors and Molluscan ACh Binding Proteins

by William R. Kem, Kristin Andrud, Galen Bruno, Hong Xing, Ferenc Soti, Todd T. Talley and Palmer Taylor

Mar. Drugs 2022, 20(1), 49; https://doi.org/10.3390/md20010049 - 04 Jan 2022

Cited by 5 | Viewed by 2352

Abstract

Nereistoxin (NTX) is a marine toxin isolated from an annelid worm that lives along the coasts of Japan. Its insecticidal properties were discovered decades ago and this stimulated the development of a variety of insecticides such as Cartap that are readily transformed into [...] Read more.

Nereistoxin (NTX) is a marine toxin isolated from an annelid worm that lives along the coasts of Japan. Its insecticidal properties were discovered decades ago and this stimulated the development of a variety of insecticides such as Cartap that are readily transformed into NTX. One unusual feature of NTX is that it is a small cyclic molecule that contains a disulfide bond. In spite of its size, it acts as an antagonist at insect and mammalian nicotinic acetylcholine receptors (nAChRs). The functional importance of the disulfide bond was assessed by determining the effects of inserting a methylene group between the two sulfur atoms, creating dimethylaminodithiane (DMA-DT). We also assessed the effect of methylating the NTX and DMA-DT dimethylamino groups on binding to three vertebrate nAChRs. Radioligand receptor binding experiments were carried out using washed membranes from rat brain and fish (Torpedo) electric organ; [³H]-cytisine displacement was used to assess binding to the predominantly high affinity alpha4beta2 nAChRs and [¹²⁵I]-alpha-bungarotoxin displacement was used to measure binding of NTX and analogs to the alpha7 and skeletal muscle type nAChRs. While the two quaternary nitrogen analogs, relative to their respective tertiary amines, displayed lower α4β2 nAChR binding affinities, both displayed much higher affinities for the Torpedo muscle nAChR and rat alpha7 brain receptors than their respective tertiary amine forms. The binding affinities of DMA-DT for the three nAChRs were lower than those of NTX and MeNTX. An AChBP mutant lacking the C loop disulfide bond that would potentially react with the NTX disulfide bond displayed an NTX affinity very similar to the parent AChBP. Inhibition of [³H]-epibatidine binding to the AChBPs was not affected by exposure to NTX or MeNTX for up to 24 hr prior to addition of the radioligand. Thus, the disulfide bond of NTX is not required to react with the vicinal disulfide in the AChBP C loop for inhibition of [³H]-epibatidine binding. However, a reversible disulfide interchange reaction of NTX with nAChRs might still occur, especially under reducing conditions. Labeled MeNTX, because it can be readily prepared with high specific radioactivity and possesses relatively high affinity for the nAChR-rich Torpedo nAChR, would be a useful probe to detect and identify any nereistoxin adducts. Full article

(This article belongs to the Special Issue Ion Channels as Marine Drug Targets 2021)

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