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Mar. Drugs, Volume 20, Issue 6 (June 2022) – 67 articles

Cover Story (view full-size image): Jellyfish are considered a nuisance for their negative effects on human health activities at sea. However, they are emerging as an alternative source of high-value compounds. In this study, we highlight that the methanolic extracts and enriched fractions from the scyphomedusa Cotylorhiza tuberculata and the cubomedusa Caryddea marsupialis reduced cell viability of specific human tumor cell lines in a dose-dependent manner. The mechanism behind the antiproliferative activity appears to be the reduction in gene expression related to apoptosis inhibition in melanoma-treated cells, which makes jellyfish a potential new source of antiproliferative drugs to be exploited in the future. View this paper
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21 pages, 6315 KiB  
Review
Progress in Isoindolone Alkaloid Derivatives from Marine Microorganism: Pharmacology, Preparation, and Mechanism
by Sijin Hang, Hui Chen, Wenhui Wu, Shiyi Wang, Yiwen Fang, Ruilong Sheng, Qidong Tu and Ruihua Guo
Mar. Drugs 2022, 20(6), 405; https://doi.org/10.3390/md20060405 - 20 Jun 2022
Cited by 9 | Viewed by 2518
Abstract
Compound 1 (SMTP-7, also FGFC1), an isoindolone alkaloid from marine fungi Starchbotrys longispora FG216 and fungi Stachybotrys microspora IFO 30018, possessed diverse bioactivities such as thrombolysis, anti-inflammatory and anti-oxidative properties, and so on. It may be widely used for the treatment of various [...] Read more.
Compound 1 (SMTP-7, also FGFC1), an isoindolone alkaloid from marine fungi Starchbotrys longispora FG216 and fungi Stachybotrys microspora IFO 30018, possessed diverse bioactivities such as thrombolysis, anti-inflammatory and anti-oxidative properties, and so on. It may be widely used for the treatment of various diseases, including cerebral infarction, stroke, ischemia/reperfusion damage, acute kidney injury, etc. Especially in cerebral infarction, compound 1 could reduce hemorrhagic transformation along with thrombolytic therapy, as the traditional therapies are accompanied with bleeding risks. In the latest studies, compound 1 selectively inhibited the growth of NSCLC cells with EGFR mutation, thus demonstrating its excellent anti-cancer activity. Herein, we summarized pharmacological activities, preparation of staplabin congeners—especially compound 1—and the mechanism of compound 1, with potential therapeutic applications. Full article
(This article belongs to the Special Issue Bio-Active Products from Mangrove Ecosystems)
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26 pages, 10436 KiB  
Review
Deep-Sea Natural Products from Extreme Environments: Cold Seeps and Hydrothermal Vents
by Mengjing Cong, Xiaoyan Pang, Kai Zhao, Yue Song, Yonghong Liu and Junfeng Wang
Mar. Drugs 2022, 20(6), 404; https://doi.org/10.3390/md20060404 - 19 Jun 2022
Cited by 13 | Viewed by 3683
Abstract
The deep sea has been proven to be a great treasure for structurally unique and biologically active natural products in the last two decades. Cold seeps and hydrothermal vents, as typical representatives of deep-sea extreme environments, have attracted more and more attention. This [...] Read more.
The deep sea has been proven to be a great treasure for structurally unique and biologically active natural products in the last two decades. Cold seeps and hydrothermal vents, as typical representatives of deep-sea extreme environments, have attracted more and more attention. This review mainly summarizes the natural products of marine animals, marine fungi, and marine bacteria derived from deep-sea cold seeps and hydrothermal vents as well as their biological activities. In general, there were 182 compounds reported, citing 132 references and covering the literature from the first report in 1984 up to March 2022. The sources of the compounds are represented by the genera Aspergillus sp., Penicillium sp., Streptomyces sp., and so on. It is worth mentioning that 90 of the 182 compounds are new and that almost 60% of the reported structures exhibited diverse bioactivities, which became attractive targets for relevant organic synthetic and biosynthetic studies. Full article
(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)
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15 pages, 1206 KiB  
Review
Algal Phlorotannins as Novel Antibacterial Agents with Reference to the Antioxidant Modulation: Current Advances and Future Directions
by Biswajita Pradhan, Rabindra Nayak, Prajna Paramita Bhuyan, Srimanta Patra, Chhandashree Behera, Sthitaprajna Sahoo, Jang-Seu Ki, Alessandra Quarta, Andrea Ragusa and Mrutyunjay Jena
Mar. Drugs 2022, 20(6), 403; https://doi.org/10.3390/md20060403 - 18 Jun 2022
Cited by 19 | Viewed by 3386
Abstract
The increasing drug resistance of infectious microorganisms is considered a primary concern of global health care. The screening and identification of natural compounds with antibacterial properties have gained immense popularity in recent times. It has previously been shown that several bioactive compounds derived [...] Read more.
The increasing drug resistance of infectious microorganisms is considered a primary concern of global health care. The screening and identification of natural compounds with antibacterial properties have gained immense popularity in recent times. It has previously been shown that several bioactive compounds derived from marine algae exhibit antibacterial activity. Similarly, polyphenolic compounds are generally known to possess promising antibacterial capacity, among other capacities. Phlorotannins (PTs), an important group of algae-derived polyphenolic compounds, have been considered potent antibacterial agents both as single drug entities and in combination with commercially available antibacterial drugs. In this context, this article reviews the antibacterial properties of polyphenols in brown algae, with particular reference to PTs. Cell death through various molecular modes of action and the specific inhibition of biofilm formation by PTs were the key discussion of this review. The synergy between drugs was also discussed in light of the potential use of PTs as adjuvants in the pharmacological antibacterial treatment. Full article
(This article belongs to the Special Issue Antimicrobial and Antiviral Agents from Marine Sources)
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15 pages, 2856 KiB  
Article
Injectable Thermosensitive Chitosan-Collagen Hydrogel as A Delivery System for Marine Polysaccharide Fucoidan
by Julia Ohmes, Lena Marie Saure, Fabian Schütt, Marie Trenkel, Andreas Seekamp, Regina Scherließ, Rainer Adelung and Sabine Fuchs
Mar. Drugs 2022, 20(6), 402; https://doi.org/10.3390/md20060402 - 18 Jun 2022
Cited by 11 | Viewed by 3664
Abstract
Fucoidans, sulfated polysaccharides from brown algae, possess multiple bioactivities in regard to osteogenesis, angiogenesis, and inflammation, all representing key molecular processes for successful bone regeneration. To utilize fucoidans in regenerative medicine, a delivery system is needed which temporarily immobilizes the polysaccharide at the [...] Read more.
Fucoidans, sulfated polysaccharides from brown algae, possess multiple bioactivities in regard to osteogenesis, angiogenesis, and inflammation, all representing key molecular processes for successful bone regeneration. To utilize fucoidans in regenerative medicine, a delivery system is needed which temporarily immobilizes the polysaccharide at the injured site. Hydrogels have become increasingly interesting biomaterials for the support of bone regeneration. Their structural resemblance with the extracellular matrix, their flexible shape, and capacity to deliver bioactive compounds or stem cells into the affected tissue make them promising materials for the support of healing processes. Especially injectable hydrogels stand out due to their minimal invasive application. In the current study, we developed an injectable thermosensitive hydrogel for the delivery of fucoidan based on chitosan, collagen, and β-glycerophosphate (β-GP). Physicochemical parameters such as gelation time, gelation temperature, swelling capacity, pH, and internal microstructure were studied. Further, human bone-derived mesenchymal stem cells (MSC) and human outgrowth endothelial cells (OEC) were cultured on top (2D) or inside the hydrogels (3D) to assess the biocompatibility. We found that the sol-gel transition occurred after approximately 1 min at 37 °C. Fucoidan integration into the hydrogel had no or only a minor impact on the mentioned physicochemical parameters compared to hydrogels which did not contain fucoidan. Release assays showed that 60% and 80% of the fucoidan was released from the hydrogel after two and six days, respectively. The hydrogel was biocompatible with MSC and OEC with a limitation for OEC encapsulation. This study demonstrates the potential of thermosensitive chitosan-collagen hydrogels as a delivery system for fucoidan and MSC for the use in regenerative medicine. Full article
(This article belongs to the Special Issue Fucoidans: From Production to Application)
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17 pages, 46576 KiB  
Article
Preparation of Ion2+-COS/SA Multifunctional Gel Films for Skin Wound Healing by an In Situ Spray Method
by Liqi Chen, Tingting Guo, Chao Shi, Kun Zhang, Shenghao Cui, Di Zhao, Faming Yang and Jingdi Chen
Mar. Drugs 2022, 20(6), 401; https://doi.org/10.3390/md20060401 - 18 Jun 2022
Cited by 2 | Viewed by 2384
Abstract
The rapid preparation of safe and efficient wound dressings that meet the needs of the entire repair process remains a major challenge for effective therapeutic wound healing. Natural, sprayable Ion2+-COS/SA multifunctional dual-network gel films created by the in situ coordination of [...] Read more.
The rapid preparation of safe and efficient wound dressings that meet the needs of the entire repair process remains a major challenge for effective therapeutic wound healing. Natural, sprayable Ion2+-COS/SA multifunctional dual-network gel films created by the in situ coordination of chitooligosaccharide (COS), metal ions and sodium alginate (SA) using casting and an in-situ spray method were synthesized. The gel films exhibited excellent physicochemical properties such as swelling, porosity and plasticity at a COS mass fraction of 3%. Furthermore, at this mass fraction, the addition of bimetallic ions led to the display of multifunctional properties, including significant antioxidant, antibacterial and cytocompatibility properties. In addition, experiments in a total skin defect model showed that this multifunctional gel film accelerates wound healing and promotes skin regeneration. These results suggest that the sprayable Ion2+-COS/SA multifunctional pro-healing gel film may be a promising candidate for the clinical treatment of allodermic wounds. Full article
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14 pages, 1433 KiB  
Article
Taeanamides A and B, Nonribosomal Lipo-Decapeptides Isolated from an Intertidal-Mudflat-Derived Streptomyces sp.
by Jinsheng Cui, Eunji Kim, Dong Hyun Moon, Tae Ho Kim, Ilnam Kang, Yeonjung Lim, Daniel Shin, Sunghoon Hwang, Young Eun Du, Myoung Chong Song, Munhyung Bae, Jang-Cheon Cho, Jichan Jang, Sang Kook Lee, Yeo Joon Yoon and Dong-Chan Oh
Mar. Drugs 2022, 20(6), 400; https://doi.org/10.3390/md20060400 - 16 Jun 2022
Cited by 3 | Viewed by 2568
Abstract
Two new lipo-decapeptides, namely taeanamides A and B (1 and 2), were discovered from the Gram-positive bacterium Streptomyces sp. AMD43, which was isolated from a mudflat sample from Anmyeondo, Korea. The exact molecular masses of 1 and 2 were revealed by [...] Read more.
Two new lipo-decapeptides, namely taeanamides A and B (1 and 2), were discovered from the Gram-positive bacterium Streptomyces sp. AMD43, which was isolated from a mudflat sample from Anmyeondo, Korea. The exact molecular masses of 1 and 2 were revealed by high-resolution mass spectrometry, and the planar structures of 1 and 2 were elucidated using NMR spectroscopy. The absolute configurations of 1 and 2 were determined using a combined analysis of 1H-1H coupling constants and ROESY correlations, the advanced Marfey’s method, and bioinformatics. The putative nonribosomal peptide synthetase pathway for the taeanamides was identified by analyzing the full genome sequence data of Streptomyces sp. AMD43. We also found that taeanamide A exhibited mild anti-tuberculosis bioactivity, whereas taeanamide B showed significant bioactivity against several cancer cell lines. Full article
(This article belongs to the Special Issue Natural Products from Marine Bacteria)
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14 pages, 16397 KiB  
Article
In Silico Virtual Screening of Marine Aldehyde Derivatives from Seaweeds against SARS-CoV-2
by Nalae Kang, Seong-Yeong Heo, Seon-Heui Cha, Ginnae Ahn and Soo-Jin Heo
Mar. Drugs 2022, 20(6), 399; https://doi.org/10.3390/md20060399 - 16 Jun 2022
Cited by 7 | Viewed by 2283
Abstract
Coronavirus disease 2019, caused by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global pandemic that poses an unprecedented threat to the global economy and human health. Several potent inhibitors targeting SARS-CoV-2 have been published; however, most of [...] Read more.
Coronavirus disease 2019, caused by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global pandemic that poses an unprecedented threat to the global economy and human health. Several potent inhibitors targeting SARS-CoV-2 have been published; however, most of them have failed in clinical trials. This study aimed to assess the therapeutic compounds among aldehyde derivatives from seaweeds as potential SARS-CoV-2 inhibitors using a computer simulation protocol. The absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties of the compounds were analyzed using a machine learning algorithm, and the docking simulation of these compounds to the 3C-like protease (Protein Data Bank (PDB) ID: 6LU7) was analyzed using a molecular docking protocol based on the CHARMm algorithm. These compounds exhibited good drug-like properties following the Lipinski and Veber rules. Among the marine aldehyde derivatives, 4-hydroxybenzaldehyde, 3-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, and 5-bromoprotocatechualdehyde were predicted to have good absorption and solubility levels and non-hepatotoxicity in the ADME/Tox prediction. 3-hydroxybenzaldehyde and 3,4-dihydroxybenzaldehyde were predicted to be non-toxic in TOPKAT prediction. In addition, 3,4-dihydroxybenzaldehyde was predicted to exhibit interactions with the 3C-like protease, with binding energies of −71.9725 kcal/mol. The computational analyses indicated that 3,4-dihydroxybenzaldehyde could be regarded as potential a SARS-CoV-2 inhibitor. Full article
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23 pages, 1268 KiB  
Review
Targeted Large-Scale Genome Mining and Candidate Prioritization for Natural Product Discovery
by Jessie James Limlingan Malit, Hiu Yu Cherie Leung and Pei-Yuan Qian
Mar. Drugs 2022, 20(6), 398; https://doi.org/10.3390/md20060398 - 16 Jun 2022
Cited by 13 | Viewed by 4669
Abstract
Large-scale genome-mining analyses have identified an enormous number of cryptic biosynthetic gene clusters (BGCs) as a great source of novel bioactive natural products. Given the sheer number of natural product (NP) candidates, effective strategies and computational methods are keys to choosing appropriate BGCs [...] Read more.
Large-scale genome-mining analyses have identified an enormous number of cryptic biosynthetic gene clusters (BGCs) as a great source of novel bioactive natural products. Given the sheer number of natural product (NP) candidates, effective strategies and computational methods are keys to choosing appropriate BGCs for further NP characterization and production. This review discusses genomics-based approaches for prioritizing candidate BGCs extracted from large-scale genomic data, by highlighting studies that have successfully produced compounds with high chemical novelty, novel biosynthesis pathway, and potent bioactivities. We group these studies based on their BGC-prioritization logics: detecting presence of resistance genes, use of phylogenomics analysis as a guide, and targeting for specific chemical structures. We also briefly comment on the different bioinformatics tools used in the field and examine practical considerations when employing a large-scale genome mining study. Full article
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51 pages, 10021 KiB  
Review
Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies
by Ricardo Ribeiro, Eugénia Pinto, Carla Fernandes and Emília Sousa
Mar. Drugs 2022, 20(6), 397; https://doi.org/10.3390/md20060397 - 15 Jun 2022
Cited by 21 | Viewed by 4665
Abstract
Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a [...] Read more.
Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (9193), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources. Full article
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28 pages, 3703 KiB  
Review
Applications of Chitosan in Surgical and Post-Surgical Materials
by Fernando Notario-Pérez, Araceli Martín-Illana, Raúl Cazorla-Luna, Roberto Ruiz-Caro and María Dolores Veiga
Mar. Drugs 2022, 20(6), 396; https://doi.org/10.3390/md20060396 - 15 Jun 2022
Cited by 15 | Viewed by 4027
Abstract
The continuous advances in surgical procedures require continuous research regarding materials with surgical applications. Biopolymers are widely studied since they usually provide a biocompatible, biodegradable, and non-toxic material. Among them, chitosan is a promising material for the development of formulations and devices with [...] Read more.
The continuous advances in surgical procedures require continuous research regarding materials with surgical applications. Biopolymers are widely studied since they usually provide a biocompatible, biodegradable, and non-toxic material. Among them, chitosan is a promising material for the development of formulations and devices with surgical applications due to its intrinsic bacteriostatic, fungistatic, hemostatic, and analgesic properties. A wide range of products has been manufactured with this polymer, including scaffolds, sponges, hydrogels, meshes, membranes, sutures, fibers, and nanoparticles. The growing interest of researchers in the use of chitosan-based materials for tissue regeneration is obvious due to extensive research in the application of chitosan for the regeneration of bone, nervous tissue, cartilage, and soft tissues. Chitosan can serve as a substance for the administration of cell-growth promoters, as well as a support for cellular growth. Another interesting application of chitosan is hemostasis control, with remarkable results in studies comparing the use of chitosan-based dressings with traditional cotton gauzes. In addition, chitosan-based or chitosan-coated surgical materials provide the formulation with antimicrobial activity that has been highly appreciated not only in dressings but also for surgical sutures or meshes. Full article
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11 pages, 681 KiB  
Article
Fast and Efficient Separation of Eleven Mycosporine-like Amino Acids by UHPLC-DAD and Their Quantification in Diverse Red Algae
by Michael Zwerger and Markus Ganzera
Mar. Drugs 2022, 20(6), 395; https://doi.org/10.3390/md20060395 - 15 Jun 2022
Cited by 6 | Viewed by 2076
Abstract
Due to their hostile habitats, characterized by a high exposure to UV-A and UV-B radiation, red algae are known to synthesize unique secondary metabolites: mycosporine-like amino acids (MAAs). These small molecules possess an extremely high UV absorption capacity and therefore mainly act as [...] Read more.
Due to their hostile habitats, characterized by a high exposure to UV-A and UV-B radiation, red algae are known to synthesize unique secondary metabolites: mycosporine-like amino acids (MAAs). These small molecules possess an extremely high UV absorption capacity and therefore mainly act as photoprotective agents. In this study, the first ultrahigh-performance liquid chromatography (UHPLC) method with diode-array detection (DAD) was developed for the determination of eleven MAAs in various algal species. All of the analytes could be separated in under 8 min on a Phenomenex Luna Omega C18 1.6 µm column. The mobile phase comprised water with 0.25% formic acid and 20 mM ammonium formate (A) and acetonitrile (B). Elution was carried out in gradient mode. Method validation following ICH guidelines confirmed excellent linearity (R2 ≥ 0.9998), selectivity, precision and accuracy (from 97.41 to 103.38%) for all analytes. The assay’s LOD was always 0.01 µg/mL; its LOQ was not higher than 0.04 µg/mL. Practical applicability was assured by analyzing several algae (e.g., Gracilaria chilensis, Pyropia plicata) using the developed method, and results indicated a high variation in MAA profiles as well as content. Whilst some MAAs were only found in specific samples, shinorine, which was always present, occurred in concentrations from 0.05 to 4.14 mg/g of dried biomass. As UHPLC-MS was also feasible, this method showed high flexibility concerning the detection mode, surpassing established procedures for MAA analysis not only concerning separation efficiency and analysis time. Full article
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8 pages, 1355 KiB  
Article
Youssoufenes A2 and A3, Antibiotic Dimeric Cinnamoyl Lipids from the ΔdtlA Mutant of a Marine-Derived Streptomyces Strain
by Jing Liu, Huayue Li, Zengzhi Liu, Tong Li, Fei Xiao and Wenli Li
Mar. Drugs 2022, 20(6), 394; https://doi.org/10.3390/md20060394 - 15 Jun 2022
Cited by 4 | Viewed by 1683
Abstract
Two new dimeric cinnamoyl lipids (CL) featuring with an unusual dearomatic carbon-bridge, named youssoufenes A2 (1) and A3 (2), were isolated from the ΔdtlA mutant strain of marine-derived Streptomyces youssoufiensis OUC6819. Structures of the isolated compounds were elucidated [...] Read more.
Two new dimeric cinnamoyl lipids (CL) featuring with an unusual dearomatic carbon-bridge, named youssoufenes A2 (1) and A3 (2), were isolated from the ΔdtlA mutant strain of marine-derived Streptomyces youssoufiensis OUC6819. Structures of the isolated compounds were elucidated based on extensive MS and NMR spectroscopic analyses, and their absolute configurations were determined by combination of the long-range NOE-based 1H-1H distance measurements and ECD calculations. Compounds 1 and 2 exhibited moderate growth inhibition against multi-drug-resistant Enterococcus faecalis CCARM 5172 with an MIC value of 22.2 μM. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Streptomyces)
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12 pages, 2871 KiB  
Article
Secondary Metabolites and Biosynthetic Gene Clusters Analysis of Deep-Sea Hydrothermal Vent-Derived Streptomyces sp. SCSIO ZS0520
by Huaran Zhang, Yingying Chen, Yanqing Li, Yongxiang Song, Junying Ma and Jianhua Ju
Mar. Drugs 2022, 20(6), 393; https://doi.org/10.3390/md20060393 - 14 Jun 2022
Cited by 6 | Viewed by 2660
Abstract
Streptomyces sp. SCSIO ZS0520 is a deep-sea hydrothermal vent-derived actinomycete. Our previous metabolism investigation showed that Streptomyces sp. SCSIO ZS0520 is a producer of cytotoxic actinopyrones. Here, another four types of secondary metabolites were identified, including six salinomycin isomers (27 [...] Read more.
Streptomyces sp. SCSIO ZS0520 is a deep-sea hydrothermal vent-derived actinomycete. Our previous metabolism investigation showed that Streptomyces sp. SCSIO ZS0520 is a producer of cytotoxic actinopyrones. Here, another four types of secondary metabolites were identified, including six salinomycin isomers (27), the macrolide elaiophylin (8), the triterpene N-acetyl-aminobacteriohopanetriol (9), and the pyrone minipyrone (10). Among them, compounds 26 and 10 are new compounds. To understand the biosynthetic pathway of these compounds, a bioinformatic analysis of the whole genome was carried out, which identified 34 secondary metabolite biosynthetic gene clusters. Next, the biosynthetic pathways responsive to four types of products were deduced on the basis of gene function predictions and structure information. Taken together, these findings prove the metabolite potential of ZS0520 and lay the foundations to solve the remaining biosynthetic issues in four types of marine natural products. Full article
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18 pages, 3911 KiB  
Article
Antitumor Properties of Epitope-Specific Engineered Vaccine in Murine Model of Melanoma
by Emiliya Stoyanova, Nikolina Mihaylova, Nikola Ralchev, Petya Ganova, Silviya Bradyanova, Iliyan Manoylov, Yuliana Raynova, Krassimira Idakieva and Andrey Tchorbanov
Mar. Drugs 2022, 20(6), 392; https://doi.org/10.3390/md20060392 - 14 Jun 2022
Viewed by 3001
Abstract
Finding new effective compounds of natural origin for composing anti-tumor vaccines is one of the main goals of antitumor research. Promising anti-cancer agents are the gastropodan hemocyanins–multimeric copper-containing glycoproteins used so far for therapy of different tumors. The properties of hemocyanins isolated from [...] Read more.
Finding new effective compounds of natural origin for composing anti-tumor vaccines is one of the main goals of antitumor research. Promising anti-cancer agents are the gastropodan hemocyanins–multimeric copper-containing glycoproteins used so far for therapy of different tumors. The properties of hemocyanins isolated from the marine snail Rapana thomasiana (RtH) and the terrestrial snail Helix aspersa (HaH) upon their use as carrier-proteins in conjugated vaccines, containing ganglioside mimotope GD3P4 peptide, were studied in the developed murine melanoma model. Murine melanoma cell line B16F10 was used for solid tumor establishment in C57BL/6 mice using various schemes of therapy. Protein engineering, flow cytometry, and cytotoxicity assays were also performed. The administration of the protein-engineered vaccines RtH-GD3P4 or HaH-GD3P4 under the three different regimens of therapy in the B16F10 murine melanoma model suppressed tumor growth, decreased tumor incidence, and prolonged the survival of treated animals. The immunization of experimental mice induced an infiltration of immunocompetent cells into the tumors and generated cytotoxic tumor-specific T cells in the spleen. The treatment also generates significantly higher levels of tumor-infiltrated M1 macrophages, compared to untreated tumor-bearing control mice. This study demonstrated a promising approach for cancer therapy having potential applications for cancer vaccine research. Full article
(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)
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8 pages, 1907 KiB  
Article
Anti-Inflammatory Effect of Sulfated Polysaccharides Isolated from Codium fragile In Vitro in RAW 264.7 Macrophages and In Vivo in Zebrafish
by Lei Wang, Jun-Geon Je, Caoxing Huang, Jae-Young Oh, Xiaoting Fu, Kaiqiang Wang, Ginnae Ahn, Jiachao Xu, Xin Gao and You-Jin Jeon
Mar. Drugs 2022, 20(6), 391; https://doi.org/10.3390/md20060391 - 13 Jun 2022
Cited by 12 | Viewed by 2464
Abstract
In this study, the anti-inflammatory activity of sulfated polysaccharides isolated from the green seaweed Codium fragile (CFCE-PS) was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results demonstrated that CFCE-PS significantly increased the viability of LPS-induced RAW 264.7 cells in a [...] Read more.
In this study, the anti-inflammatory activity of sulfated polysaccharides isolated from the green seaweed Codium fragile (CFCE-PS) was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results demonstrated that CFCE-PS significantly increased the viability of LPS-induced RAW 264.7 cells in a concentration-dependent manner. CFCE-PS remarkably and concentration-dependently reduced the levels of inflammatory molecules including prostaglandin E2, nitric oxide (NO), interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 in LPS-stimulated RAW 264.7 cells. In addition, in vivo test results indicated that CFCE-PS effectively reduced reactive oxygen species, cell death, and NO levels in LPS-stimulated zebrafish. Thus, these results indicate that CFCE-PS possesses in vitro and in vivo anti-inflammatory activities and suggest it is a potential ingredient in the functional food and pharmaceutical industries. Full article
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17 pages, 3069 KiB  
Article
A Paternal Fish Oil Diet Preconception Modulates the Gut Microbiome and Attenuates Necrotizing Enterocolitis in Neonatal Mice
by Jelonia T. Rumph, Victoria R. Stephens, Sharareh Ameli, Philip N. Gaines, Kevin G. Osteen, Kaylon L. Bruner-Tran and Pius N. Nde
Mar. Drugs 2022, 20(6), 390; https://doi.org/10.3390/md20060390 - 13 Jun 2022
Cited by 2 | Viewed by 2477
Abstract
Epidemiology and animal studies suggest that a paternal history of toxicant exposure contributes to the developmental origins of health and disease. Using a mouse model, our laboratory previously reported that a paternal history of in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased his offspring’s [...] Read more.
Epidemiology and animal studies suggest that a paternal history of toxicant exposure contributes to the developmental origins of health and disease. Using a mouse model, our laboratory previously reported that a paternal history of in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased his offspring’s risk of developing necrotizing enterocolitis (NEC). Additionally, our group and others have found that formula supplementation also increases the risk of NEC in both humans and mice. Our murine studies revealed that intervening with a paternal fish oil diet preconception eliminated the TCDD-associated outcomes that are risk factors for NEC (e.g., intrauterine growth restriction, delayed postnatal growth, and preterm birth). However, the efficacy of a paternal fish oil diet in eliminating the risk of disease development in his offspring was not investigated. Herein, reproductive-age male mice exposed to TCDD in utero were weaned to a standard or fish oil diet for one full cycle of spermatogenesis, then mated to age-matched unexposed females. Their offspring were randomized to a strict maternal milk diet or a supplemental formula diet from postnatal days 7–10. Offspring colon contents and intestines were collected to determine the onset of gut dysbiosis and NEC. We found that a paternal fish oil diet preconception reduced his offspring’s risk of toxicant-driven NEC, which was associated with a decrease in the relative abundance of the Firmicutes phylum, but an increase in the relative abundance of the Negativicutes class. Full article
(This article belongs to the Special Issue Pre-clinical Marine Drug Discovery Ⅱ)
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14 pages, 3387 KiB  
Review
Updated Trends on the Biodiscovery of New Marine Natural Products from Invertebrates
by Ricardo Calado, Renato Mamede, Sónia Cruz and Miguel C. Leal
Mar. Drugs 2022, 20(6), 389; https://doi.org/10.3390/md20060389 - 09 Jun 2022
Cited by 9 | Viewed by 2891
Abstract
From 1990–2019, a total of 15,442 New Marine Natural Products from Invertebrates (NMNPIs) were reported. The 2010s saw the most prolific decade of biodiscovery, with 5630 NMNPIs recorded. The phyla that contributed most biomolecules were the Porifera (sponges) (47.2%, 2659 NMNPIs) and the [...] Read more.
From 1990–2019, a total of 15,442 New Marine Natural Products from Invertebrates (NMNPIs) were reported. The 2010s saw the most prolific decade of biodiscovery, with 5630 NMNPIs recorded. The phyla that contributed most biomolecules were the Porifera (sponges) (47.2%, 2659 NMNPIs) and the Cnidaria (35.3%, 1989 NMNPIs). The prevalence of these two phyla as the main sources of NMNPIs became more pronounced in the 2010s. The tropical areas of the Pacific Ocean yielded more NMNPIs, most likely due to the remarkable biodiversity of coral reefs. The Indo-Burma biodiversity hotspot (BH) was the most relevant area for the biodiscovery of NMNPIs in the 2010s, accounting for nearly one-third (1819 NMNPIs) of the total and surpassing the top BH from the 1990s and the 2000s (the Sea of Japan and the Caribbean Islands, respectively). The Chinese exclusive economic zone (EEZ) alone contributed nearly one-quarter (24.7%) of all NMNPIs recorded during the 2010s, displacing Japan’s leading role from the 1990s and the 2000s. With the biodiscovery of these biomolecules steadily decreasing since 2012, it is uncertain whether this decline has been caused by lower bioprospecting efforts or the potential exhaustion of chemodiversity from traditional marine invertebrate sources. Full article
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13 pages, 1538 KiB  
Article
Genome Analysis of a Novel Polysaccharide-Degrading Bacterium Paenibacillus algicola and Determination of Alginate Lyases
by Huiqin Huang, Zhiguo Zheng, Xiaoxiao Zou, Zixu Wang, Rong Gao, Jun Zhu, Yonghua Hu and Shixiang Bao
Mar. Drugs 2022, 20(6), 388; https://doi.org/10.3390/md20060388 - 09 Jun 2022
Cited by 4 | Viewed by 2477
Abstract
Carbohydrate-active enzymes (CAZymes) are an important characteristic of bacteria in marine systems. We herein describe the CAZymes of Paenibacillus algicola HB172198T, a novel type species isolated from brown algae in Qishui Bay, Hainan, China. The genome of strain HB172198T is [...] Read more.
Carbohydrate-active enzymes (CAZymes) are an important characteristic of bacteria in marine systems. We herein describe the CAZymes of Paenibacillus algicola HB172198T, a novel type species isolated from brown algae in Qishui Bay, Hainan, China. The genome of strain HB172198T is a 4,475,055 bp circular chromosome with an average GC content of 51.2%. Analysis of the nucleotide sequences of the predicted genes shows that strain HB172198T encodes 191 CAZymes. Abundant putative enzymes involved in the degradation of polysaccharides were identified, such as alginate lyase, agarase, carrageenase, xanthanase, xylanase, amylases, cellulase, chitinase, fucosidase and glucanase. Four of the putative polysaccharide lyases from families 7, 15 and 38 were involved in alginate degradation. The alginate lyases of strain HB172198T exhibited the maximum activity 152 U/mL at 50 °C and pH 8.0, and were relatively stable at pH 7.0 and temperatures lower than 40 °C. The average degree of polymerization (DP) of the sodium alginate oligosaccharide (AOS) degraded by the partially purified alginate lyases remained around 14.2, and the thin layer chromatography (TCL) analysis indicated that it contained DP2-DP8 oligosaccharides. The complete genome sequence of P. algicola HB172198T will enrich our knowledge of the mechanism of polysaccharide lyase production and provide insights into its potential applications in the degradation of polysaccharides such as alginate. Full article
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22 pages, 980 KiB  
Review
Call the Eckols: Present and Future Potential Cancer Therapies
by Pedro Monteiro, Silvia Lomartire, João Cotas, João C. Marques, Leonel Pereira and Ana M. M. Gonçalves
Mar. Drugs 2022, 20(6), 387; https://doi.org/10.3390/md20060387 - 09 Jun 2022
Cited by 9 | Viewed by 2577
Abstract
In recent years, an increased interest in marine macroalgae bioactive compounds has been recorded due to their benefits to human health and welfare. Several of their bioactivities have been demonstrated, such as anti-inflammatory, antioxidant, anticarcinogenic, antibacterial and antiviral behavior. However, there still lacks [...] Read more.
In recent years, an increased interest in marine macroalgae bioactive compounds has been recorded due to their benefits to human health and welfare. Several of their bioactivities have been demonstrated, such as anti-inflammatory, antioxidant, anticarcinogenic, antibacterial and antiviral behavior. However, there still lacks a clear definition regarding how these compounds exert their bioactive properties. Of all the bioactive compounds derived from marine macroalgae, attention has been focused on phenolic compounds, specifically in phlorotannins, due to their potential for biomedical applications. Phlorotannins are a diverse and wide group of phenolic compounds, with several structural variations based on the monomer phloroglucinol. Among the diverse phlorotannin structures, the eckol-family of phlorotannins demonstrates remarkable bioactivity, notably their anti-tumoral properties. However, the molecular mechanisms by which this activity is achieved remain elusive and sparse. This review focuses on the described molecular mechanisms of anti-tumoral effects by the eckol family of compounds and the future prospects of these molecules for potential application in oncology therapies. Full article
(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)
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27 pages, 2716 KiB  
Review
Antitumor Potential of Immunomodulatory Natural Products
by Genoveffa Nuzzo, Giuseppina Senese, Carmela Gallo, Federica Albiani, Lucia Romano, Giuliana d’Ippolito, Emiliano Manzo and Angelo Fontana
Mar. Drugs 2022, 20(6), 386; https://doi.org/10.3390/md20060386 - 08 Jun 2022
Cited by 16 | Viewed by 3762
Abstract
Cancer is one of the leading causes of death globally. Anticancer drugs aim to block tumor growth by killing cancerous cells in order to prevent tumor progression and metastasis. Efficient anticancer drugs should also minimize general toxicity towards organs and healthy cells. Tumor [...] Read more.
Cancer is one of the leading causes of death globally. Anticancer drugs aim to block tumor growth by killing cancerous cells in order to prevent tumor progression and metastasis. Efficient anticancer drugs should also minimize general toxicity towards organs and healthy cells. Tumor growth can also be successfully restrained by targeting and modulating immune response. Cancer immunotherapy is assuming a growing relevance in the fight against cancer and has recently aroused much interest for its wider safety and the capability to complement conventional chemotherapeutic approaches. Natural products are a traditional source of molecules with relevant potential in the pharmacological field. The huge structural diversity of metabolites with low molecular weight (small molecules) from terrestrial and marine organisms has provided lead compounds for the discovery of many modern anticancer drugs. Many natural products combine chemo-protective and immunomodulant activity, thus offering the potential to be used alone or in association with conventional cancer therapy. In this review, we report the natural products known to possess antitumor properties by interaction with immune system, as well as discuss the possible immunomodulatory mechanisms of these molecules. Full article
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30 pages, 1069 KiB  
Review
Antiviral Activity and Mechanisms of Seaweeds Bioactive Compounds on Enveloped Viruses—A Review
by Silvia Lomartire and Ana M. M. Gonçalves
Mar. Drugs 2022, 20(6), 385; https://doi.org/10.3390/md20060385 - 08 Jun 2022
Cited by 19 | Viewed by 2934
Abstract
In the last decades, the interest in seaweed has significantly increased. Bioactive compounds from seaweed’s currently receive major attention from pharmaceutical companies as they express several interesting biological activities which are beneficial for humans. The structural diversity of seaweed metabolites provides diverse biological [...] Read more.
In the last decades, the interest in seaweed has significantly increased. Bioactive compounds from seaweed’s currently receive major attention from pharmaceutical companies as they express several interesting biological activities which are beneficial for humans. The structural diversity of seaweed metabolites provides diverse biological activities which are expressed through diverse mechanisms of actions. This review mainly focuses on the antiviral activity of seaweed’s extracts, highlighting the mechanisms of actions of some seaweed molecules against infection caused by different types of enveloped viruses: influenza, Lentivirus (HIV-1), Herpes viruses, and coronaviruses. Seaweed metabolites with antiviral properties can act trough different pathways by increasing the host’s defense system or through targeting and blocking virus replication before it enters host cells. Several studies have already established the large antiviral spectrum of seaweed’s bioactive compounds. Throughout this review, antiviral mechanisms and medical applications of seaweed’s bioactive compounds are analyzed, suggesting seaweed’s potential source of antiviral compounds for the formulation of novel and natural antiviral drugs. Full article
(This article belongs to the Special Issue The Mechanisms of Action of Bioactive Marine Natural Products)
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31 pages, 2450 KiB  
Review
Seaweed-Derived Phlorotannins: A Review of Multiple Biological Roles and Action Mechanisms
by Fazlurrahman Khan, Geum-Jae Jeong, Mohd Sajjad Ahmad Khan, Nazia Tabassum and Young-Mog Kim
Mar. Drugs 2022, 20(6), 384; https://doi.org/10.3390/md20060384 - 08 Jun 2022
Cited by 22 | Viewed by 3670
Abstract
Phlorotannins are a group of phenolic secondary metabolites isolated from a variety of brown algal species belonging to the Fucaceae, Sargassaceae, and Alariaceae families. The isolation of phlorotannins from various algal species has received a lot of interest owing to the fact that [...] Read more.
Phlorotannins are a group of phenolic secondary metabolites isolated from a variety of brown algal species belonging to the Fucaceae, Sargassaceae, and Alariaceae families. The isolation of phlorotannins from various algal species has received a lot of interest owing to the fact that they have a range of biological features and are very biocompatible in their applications. Phlorotannins have a wide range of therapeutic biological actions, including antimicrobial, antidiabetic, antioxidant, anticancer, anti-inflammatory, anti-adipogenesis, and numerous other biomedical applications. The current review has extensively addressed the application of phlorotannins, which have been extensively investigated for the above-mentioned biological action and the underlying mechanism of action. Furthermore, the current review offers many ways to use phlorotannins to avoid certain downsides, such as low stability. This review article will assist the scientific community in investigating the greater biological significance of phlorotannins and developing innovative techniques for treating both infectious and non-infectious diseases in humans. Full article
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19 pages, 4153 KiB  
Article
Marine Chitooligosaccharide Alters Intestinal Flora Structure and Regulates Hepatic Inflammatory Response to Influence Nonalcoholic Fatty Liver Disease
by Jiayao Feng, Yongjian Liu, Jiajia Chen, Yan Bai, Jincan He, Hua Cao, Qishi Che, Jiao Guo and Zhengquan Su
Mar. Drugs 2022, 20(6), 383; https://doi.org/10.3390/md20060383 - 07 Jun 2022
Cited by 12 | Viewed by 2286
Abstract
In this study, C57BL/6 mice were given an HFHSD diet for 8 weeks to induce hepatic steatosis and then given COSM solution orally for 12 weeks. The study found that the HFHSD diet resulted in steatosis and insulin resistance in mice. The formation [...] Read more.
In this study, C57BL/6 mice were given an HFHSD diet for 8 weeks to induce hepatic steatosis and then given COSM solution orally for 12 weeks. The study found that the HFHSD diet resulted in steatosis and insulin resistance in mice. The formation of NAFLD induced by HFHSD diet was related to the imbalance of intestinal flora. However, after COSM intervention, the abundance of beneficial bacteria increased significantly, while the abundance of harmful bacteria decreased significantly. The HFHSD diet also induced changes in intestinal bacterial metabolites, and the content of short-chain fatty acids in cecal contents after COSM intervention was significantly higher than that in the model group. In addition, COSM not only improved LPS levels and barrier dysfunction in the ileum and colon but upregulated protein levels of ZO-1, occludin, and claudin in the colon and downregulated the liver LPS/TLR4/NF-κB inflammatory pathway. We concluded that the treatment of marine chitooligosaccharide COSM could improve the intestinal microflora structure of the fatty liver and activate an inflammatory signaling pathway, thus alleviating the intrahepatic lipid accumulation induced by HFHSD. Full article
(This article belongs to the Special Issue Poly- and Oligosaccharides from Marine Origins)
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17 pages, 4965 KiB  
Article
Increased Sulfation in Gracilaria fisheri Sulfated Galactans Enhances Antioxidant and Antiurolithiatic Activities and Protects HK-2 Cell Death Induced by Sodium Oxalate
by Waraporn Sakaew, Jenjiralai Phanphak, Somsuda Somintara, Wiphawi Hipkaeo, Kanokpan Wongprasert, José Kovensky, Choowadee Pariwatthanakun and Tawut Rudtanatip
Mar. Drugs 2022, 20(6), 382; https://doi.org/10.3390/md20060382 - 07 Jun 2022
Cited by 1 | Viewed by 2066
Abstract
Urolithiasis is a common urological disease characterized by the presence of a stone anywhere along the urinary tract. The major component of such stones is calcium oxalate, and reactive oxygen species act as an essential mediator of calcium oxalate crystallization. Previous studies have [...] Read more.
Urolithiasis is a common urological disease characterized by the presence of a stone anywhere along the urinary tract. The major component of such stones is calcium oxalate, and reactive oxygen species act as an essential mediator of calcium oxalate crystallization. Previous studies have demonstrated the antioxidant and antiurolithiatic activities of sulfated polysaccharides. In this study, native sulfated galactans (N-SGs) with a molecular weight of 217.4 kDa from Gracilaria fisheri were modified to obtain lower molecular weight SG (L-SG) and also subjected to sulfation SG (S-SG). The in vitro antioxidant and antiurolithiatic activities of the modified substances and their ability to protect against sodium oxalate-induced renal tubular (HK-2) cell death were investigated. The results revealed that S-SG showed more pronounced antioxidant activities (DPPH and O2 scavenging activities) than those of other compounds. S-SG exhibited the highest antiurolithiatic activity in terms of nucleation and aggregation, as well as crystal morphology and size. Moreover, S-SG showed improved cell survival and increased anti-apoptotic BCL-2 protein in HK-2 cells treated with sodium oxalate. Our findings highlight the potential application of S-SG in the functional food and pharmaceutical industries. Full article
(This article belongs to the Special Issue Sulfur-Containing Marine Bioactives 2.0)
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12 pages, 2393 KiB  
Article
New Cladiellin-Type Diterpenoids from the South China Sea Soft Coral Cladiella krempfi: Structures and Molecular Docking Analysis in EGFRs
by Yang Jin, Li-Gong Yao, Yue-Wei Guo and Xu-Wen Li
Mar. Drugs 2022, 20(6), 381; https://doi.org/10.3390/md20060381 - 07 Jun 2022
Cited by 3 | Viewed by 1794
Abstract
Two new cladiellin-type diterpenoids (1 and 2) and four known related compounds 36, were isolated from the South China Sea soft coral Cladiella krempfi. Compound 2 is the third example of cladiellins of an unusual peroxy group [...] Read more.
Two new cladiellin-type diterpenoids (1 and 2) and four known related compounds 36, were isolated from the South China Sea soft coral Cladiella krempfi. Compound 2 is the third example of cladiellins of an unusual peroxy group in the C-6 position in C. krempfi. The structures and absolute configurations of the new compounds were established by extensive spectroscopic analysis, X-ray diffraction, and/or chemical correlation. In bioassay, all the compounds were evaluated for cytotoxicity and epidermal growth factor receptor (EGFR) inhibitory activity. A molecular docking experiment was conducted to study the structure–activity relationship of cladiellin-type diterpenoids on EGFR inhibitory activity. Full article
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13 pages, 2328 KiB  
Article
Fucose-Rich Sulfated Polysaccharides from Two Vietnamese Sea Cucumbers Bohadschia argus and Holothuria (Theelothuria) spinifera: Structures and Anticoagulant Activity
by Nadezhda E. Ustyuzhanina, Maria I. Bilan, Andrey S. Dmitrenok, Eugenia A. Tsvetkova, Sofya P. Nikogosova, Cao Thi Thuy Hang, Pham Duc Thinh, Dinh Thanh Trung, Tran Thi Thanh Van, Alexander S. Shashkov, Anatolii I. Usov and Nikolay E. Nifantiev
Mar. Drugs 2022, 20(6), 380; https://doi.org/10.3390/md20060380 - 06 Jun 2022
Cited by 13 | Viewed by 2072
Abstract
Fucosylated chondroitin sulfates (FCSs) FCS-BA and FCS-HS, as well as fucan sulfates (FSs) FS-BA-AT and FS-HS-AT were isolated from the sea cucumbers Bohadschia argus and Holothuria (Theelothuria) spinifera, respectively. Purification of the polysaccharides was carried out by anion-exchange chromatography on DEAE-Sephacel [...] Read more.
Fucosylated chondroitin sulfates (FCSs) FCS-BA and FCS-HS, as well as fucan sulfates (FSs) FS-BA-AT and FS-HS-AT were isolated from the sea cucumbers Bohadschia argus and Holothuria (Theelothuria) spinifera, respectively. Purification of the polysaccharides was carried out by anion-exchange chromatography on DEAE-Sephacel column. Structural characterization of polysaccharides was performed in terms of monosaccharide and sulfate content, as well as using a series of non-destructive NMR spectroscopic methods. Both FCSs were shown to contain a chondroitin core [→3)-β-d-GalNAc-(1→4)-β-d-GlcA-(1→]n bearing sulfated fucosyl branches at O-3 of every GlcA residue in the chain. These fucosyl residues were different in pattern of sulfation: FCS-BA contained Fuc2S4S, Fuc3S4S and Fuc4S at a ratio of 1:8:2, while FCS-HS contained these residues at a ratio of 2:2:1. Polysaccharides differed also in content of GalNAc4S6S and GalNAc4S units, the ratios being 14:1 for FCS-BA and 4:1 for FCS-HS. Both FCSs demonstrated significant anticoagulant activity in clotting time assay and potentiated inhibition of thrombin, but not of factor Xa. FS-BA-AT was shown to be a regular linear polymer of 4-linked α-L-fucopyranose 3-sulfate, the structure being confirmed by NMR spectra of desulfated polysaccharide. In spite of considerable sulfate content, FS-BA-AT was practically devoid of anticoagulant activity. FS-HS-AT cannot be purified completely from contamination of some FCS. Its structure was tentatively represented as a mixture of chains identical with FS-BA-AT and other chains built up of randomly sulfated alternating 4- and 3-linked α-L-fucopyranose residues. Full article
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21 pages, 2436 KiB  
Article
Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents
by Shimei Xiao, Zhiqiang Wang, Huanli Zhang, Lei Zhao, Qingran Chang, Xiong Zhang, Rui Yan, Xiaodan Wu and Yingxue Jin
Mar. Drugs 2022, 20(6), 379; https://doi.org/10.3390/md20060379 - 05 Jun 2022
Cited by 12 | Viewed by 1904
Abstract
The methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron transfer cyclization reaction. It was [...] Read more.
The methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron transfer cyclization reaction. It was found that the single-methyl substitution was beneficial for the bioactivity of cyclic analogs with isoindolinone fragments, and the influence of methylation on bioactivity is uncertain and is sometimes case-specific. The compound with a single methyl group at Gly5 (compound 8) showed the strongest antiproliferative activity against HepG-2 cells. The tumor cell apoptosis, cell cycle, mitochondrial membrane potential, intracellular Ca2+ concentration and lactate dehydrogenase activity have been studied extensively to evaluate the antitumor potential of compound 8. Western blotting tests showed that compound 8 could decrease the MDM2 level and increase p53 levels efficiently. Careful molecular docking suggested that cyclic peptide 8 could bind firmly with MDM2 oncoprotein, indicating that MDM2 may be a potential drug target of the prepared peptides. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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14 pages, 2196 KiB  
Article
Oncolytic Vaccinia Virus Harboring Aphrocallistes vastus Lectin Inhibits the Growth of Hepatocellular Carcinoma Cells
by Riqing Jiang, Yufeng Qiu, Xiaomei Zhang, Ningning Zhou, Xiaoyuan Jia, Kan Chen, Yanrong Zhou, Ting Ye and Gongchu Li
Mar. Drugs 2022, 20(6), 378; https://doi.org/10.3390/md20060378 - 04 Jun 2022
Cited by 5 | Viewed by 2251
Abstract
Oncolytic vaccinia virus has been developed as a novel cancer therapeutic drug in recent years. Our previous studies demonstrated that the antitumor effect of oncolytic vaccina virus harboring Aphrocallistes vastus lectin (oncoVV-AVL) was significantly enhanced in several cancer cells. In the present study, [...] Read more.
Oncolytic vaccinia virus has been developed as a novel cancer therapeutic drug in recent years. Our previous studies demonstrated that the antitumor effect of oncolytic vaccina virus harboring Aphrocallistes vastus lectin (oncoVV-AVL) was significantly enhanced in several cancer cells. In the present study, we investigated the underlying mechanisms of AVL that affect virus replication and promote the antitumor efficacy of oncolytic virus in hepatocellular carcinoma (HCC). Our results showed that oncoVV-AVL markedly exhibited antitumor effects in both hepatocellular carcinoma cell lines and a xenograft mouse model. Further investigation illustrated that oncoVV-AVL could activate tumor immunity by upregulating the expression of type I interferons and enhance virus replication by inhibiting ISRE mediated viral defense response. In addition, we inferred that AVL promoted the ability of virus replication by regulating the PI3K/Akt, MAPK/ERK, and Hippo/MST pathways through cross-talk Raf-1, as well as metabolism-related pathways. These findings provide a novel perspective for the exploitation of marine lectins in oncolytic therapy. Full article
(This article belongs to the Special Issue Marine Lectins)
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19 pages, 3084 KiB  
Article
A Fucan Sulfate with Pentasaccharide Repeating Units from the Sea Cucumber Holothuriafloridana and Its Anticoagulant Activity
by Zimo Ning, Pin Wang, Zhichuang Zuo, Xuelin Tao, Li Gao, Chen Xu, Zhiyue Wang, Bin Wu, Na Gao and Jinhua Zhao
Mar. Drugs 2022, 20(6), 377; https://doi.org/10.3390/md20060377 - 03 Jun 2022
Cited by 9 | Viewed by 1812
Abstract
A fucan sulfate (HfFS) was isolated from the sea cucumber Holothuriafloridana after proteolysis-alkaline treatment and purified with anion-exchange chromatography. The molecular weight (Mw) of HfFS was determined to be 443.4 kDa, and the sulfate content of HfFS was 30.4%. The structural analysis [...] Read more.
A fucan sulfate (HfFS) was isolated from the sea cucumber Holothuriafloridana after proteolysis-alkaline treatment and purified with anion-exchange chromatography. The molecular weight (Mw) of HfFS was determined to be 443.4 kDa, and the sulfate content of HfFS was 30.4%. The structural analysis of the peroxidative depolymerized product (dHfFS-1) showed that the primary structure of HfFS was mainly composed of a distinct pentasaccharide repeating unit -[l-Fuc2S4S-α(1,3)-l-Fuc-α(1,3)-Fuc-α(1,3)-l-Fuc2S-α(1,3)-l-Fuc2S-α(1,3)-]n-. Then, the “bottom-up” strategy was employed to confirm the structure of HfFS, and a series of fucooligosaccharides (disaccharides, trisaccharides, and tetrasaccharides) were purified from the mild acid-hydrolyzed HfFS. The structures identified through 1D/2D NMR spectra showed that these fucooligosaccharides could be derivates from the pentasaccharide units, while the irregular sulfate substituent also exists in the units. Anticoagulant activity assays of native HfFS and its depolymerized products (dHf-1~dHf-6) in vitro suggested that HfFS exhibits potent APTT-prolonging activity and the potencies decreased with the reduction in molecular weights, and HfFS fragments (dHf-4~dHf-6) with Mw less than 11.5 kDa showed no significant anticoagulant effect. Overall, our study enriched the knowledge about the structural diversity of FSs in different sea cucumber species and their biological activities. Full article
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14 pages, 6691 KiB  
Article
Comparison of Physicochemical and Structural Properties of Acid-Soluble and Pepsin-Soluble Collagens from Blacktip Reef Shark Skin
by Baolin Ge, Chunyu Hou, Bin Bao, Zhilin Pan, José Eduardo Maté Sánchez de Val, Jeevithan Elango and Wenhui Wu
Mar. Drugs 2022, 20(6), 376; https://doi.org/10.3390/md20060376 - 02 Jun 2022
Cited by 6 | Viewed by 2422
Abstract
Fish collagen has been widely used in tissue engineering (TE) applications as an implant, which is generally transplanted into target tissue with stem cells for better regeneration ability. In this case, the success rate of this research depends on the fundamental components of [...] Read more.
Fish collagen has been widely used in tissue engineering (TE) applications as an implant, which is generally transplanted into target tissue with stem cells for better regeneration ability. In this case, the success rate of this research depends on the fundamental components of fish collagen such as amino acid composition, structural and rheological properties. Therefore, researchers have been trying to find an innovative raw material from marine origins for tissue engineering applications. Based on this concept, collagens such as acid-soluble (ASC) and pepsin-soluble (PSC) were extracted from a new type of cartilaginous fish, the blacktip reef shark, for the first time, and were further investigated for physicochemical, protein pattern, microstructural and peptide mapping. The study results confirmed that the extracted collagens resemble the protein pattern of type-I collagen comprising the α1, α2, β and γ chains. The hydrophobic amino acids were dominant in both collagens with glycine and hydroxyproline as major amino acids. From the FTIR spectra, α helix (27.72 and 26.32%), β-sheet (22.24 and 23.35%), β-turn (21.34 and 22.08%), triple helix (14.11 and 14.13%) and random coil (14.59 and 14.12%) structures of ASC and PSC were confirmed, respectively. Collagens retained their triple helical and secondary structure well. Both collagens had maximum solubility at 3% NaCl and pH 4, and had absorbance maxima at 234 nm, respectively. The peptide mapping was almost similar for ASC and PSC at pH 2, generating peptides ranging from 15 to 200 kDa, with 23 kDa as a major peptide fragment. The microstructural analysis confirmed the homogenous fibrillar nature of collagens with more interconnected networks. Overall, the preset study concluded that collagen can be extracted more efficiently without disturbing the secondary structure by pepsin treatment. Therefore, the blacktip reef shark skin could serve as a potential source for collagen extraction for the pharmaceutical and biomedical applications. Full article
(This article belongs to the Special Issue Biomedical and Pharmacological Applications of Marine Collagen)
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