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Marine Drugs
Special Issues
Screening for Marine Natural Products with Potential as Chemotherapeutics
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Screening for Marine Natural Products with Potential as Chemotherapeutics

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (20 February 2020) | Viewed by 19903

Special Issue Editors

Prof. Dr. Espen Hansen

E-Mail Website
Guest Editor
Marbio, UiT The Arctic University of Norway, Breivika, N-9037 Tromsø, Norway
Interests: bioactive natural products; mass spectrometry; chromatography; metabolomics; bioactivity screening
Special Issues, Collections and Topics in MDPI journals
Prof. Jeanette Hammer Andersen

E-Mail Website
Guest Editor
Marbio, UiT The Arctic University of Norway, Breivika, N-9037 Tromsø, Norway
Interests: bioactive natural products; bioactivity screening; high-throughput cell-based assays; anticancer and antibacterial natural products

Special Issue Information

Dear Colleagues,

Marine natural products have a long history as chemotherapeutics. Cytarabine, a nucleoside analog derived from spongothymidine isolated from the sponge Cryptotethia crypta, was approved by the FDA for the treatment of leukemia as early as 1969. Over the years, anticancer screening has been an important part of numerous marine natural products drug discovery programs, both in the academia and industry. The efforts of the Developmental Therapeutics Program of the National Cancer Institute, in the USA, including their extensive screening using the famous 60-cell line panel, is maybe the most prominent example of how anticancer screening has promoted the field of natural products research.

Screening for compounds with potential as chemotherapeutics remains an important part of many marine biodiscovery projects. The screening can be approached in many different ways, but screening for reduced viability of cancer cell lines as measured by reductions in cellular respiration is still the most frequently reported method. However, other approaches, such as target-based screening and high-content screening, offers other advantages for identifying natural products with anticancer properties. The screening can be used to characterize potential anticancer properties of pure compounds, crude extracts or fractions, but it is also frequently used to track bioactivity during isolation of unknown bioactive compounds from complex extracts (i.e., bioactivity-guided fractionation).

In this Special Issue of Marine Drugs, we welcome submission of manuscripts for original research papers, reviews and opinion papers describing screening of marine natural products with potential as chemotherapeutics.

Prof. Espen Hansen
Prof. Jeanette Hammer Andersen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cell based screening
  • Phenotypic screening
  • Target based screening
  • Anticancer
  • Cancer cell lines
  • Chemotherapeutics
  • Marine natural products

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Published Papers (5 papers)

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Research

12 pages, 3872 KiB  
Article
Dechdigliotoxins A–C, Three Novel Disulfide-Bridged Gliotoxin Dimers from Deep-Sea Sediment Derived Fungus Dichotomomyces cejpii
by Zhaoming Liu, Zhen Fan, Zhanghua Sun, Hongxin Liu and Weimin Zhang
Mar. Drugs 2019, 17(11), 596; https://doi.org/10.3390/md17110596 - 23 Oct 2019
Cited by 11 | Viewed by 2391
Abstract
Dechdigliotoxins A–C (1–3), which represented the first examples of gliotoxin dimers with an unprecedented exocyclic disulfide linkage, were obtained from a deep-sea derived fungus Dichotomomyces cejpii FS110. The structures of these compounds were elucidated on the basis of spectroscopic analysis and [...] Read more.
Dechdigliotoxins A–C (1–3), which represented the first examples of gliotoxin dimers with an unprecedented exocyclic disulfide linkage, were obtained from a deep-sea derived fungus Dichotomomyces cejpii FS110. The structures of these compounds were elucidated on the basis of spectroscopic analysis and the absolute configurations were unambiguously determined through quantum chemical calculations, as well as DP4+ probability simulations. The proposed biosynthetic pathway suggested 1–3 were generated from unusual L-Phe and D-Ser. All the isolates were evaluated for their cytotoxicity against four tumor cell lines. Full article
(This article belongs to the Special Issue Screening for Marine Natural Products with Potential as Chemotherapeutics)
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14 pages, 1853 KiB  
Article
Indole-4-carboxaldehyde Isolated from Seaweed, Sargassum thunbergii, Attenuates Methylglyoxal-Induced Hepatic Inflammation
by Seon-Heui Cha, Yongha Hwang, Soo-Jin Heo and Hee-Sook Jun
Mar. Drugs 2019, 17(9), 486; https://doi.org/10.3390/md17090486 - 21 Aug 2019
Cited by 13 | Viewed by 3944
Abstract
Glucose degradation is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Glyoxalase-1 (Glo-1) is a ubiquitous cellular enzyme that participates in the detoxification of methylglyoxal (MGO), a cytotoxic byproduct of glycolysis that induces protein modification (advanced glycation end-products, AGEs) [...] Read more.
Glucose degradation is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Glyoxalase-1 (Glo-1) is a ubiquitous cellular enzyme that participates in the detoxification of methylglyoxal (MGO), a cytotoxic byproduct of glycolysis that induces protein modification (advanced glycation end-products, AGEs) and inflammation. Here, we investigated the anti-inflammatory effect of indole-4-carboxaldehyde (ST-I4C), which was isolated from the edible seaweed Sargassum thunbergii, on MGO-induced inflammation in HepG2 cells, a human hepatocyte cell line. ST-I4C attenuated the MGO-induced expression of inflammatory-related genes, such as tumor necrosis factor (TNF)-α and IFN-γ by activating nuclear factor-kappa B (NF-κB) without toxicity in HepG2 cells. In addition, ST-I4C reduced the MGO-induced AGE formation and the expression of the receptor for AGE (RAGE). Interestingly, both the mRNA and protein expression levels of Glo-1 increased following ST-I4C treatment, and the decrease in Glo-1 mRNA expression caused by MGO exposure was rescued by ST-I4C pretreatment. These results suggest that ST-I4C shows anti-inflammatory activity against MGO-induced inflammation in human hepatocytes by preventing an increase in the pro-inflammatory gene expression and AGE formation. Therefore, it represents a potential therapeutic agent for the prevention of hepatic steatosis. Full article
(This article belongs to the Special Issue Screening for Marine Natural Products with Potential as Chemotherapeutics)
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19 pages, 2162 KiB  
Article
Anti-Thrombin, Anti-Adhesive, Anti-Migratory, and Anti-Proliferative Activities of Sulfated Galactans from the Tropical Green Seaweed, Udotea flabellum
by Maxsuell Lucas Mendes Marques, Fernando Bastos Presa, Rony Lucas Silva Viana, Mariana Santana Santos Pereira Costa, Monica Oliveira Rocha Amorim, Daniel Lima Bellan, Monique Gabriela Chagas Faustino Alves, Leandro Silva Costa, Edvaldo Silva Trindade and Hugo Alexandre Oliveira Rocha
Mar. Drugs 2019, 17(1), 5; https://doi.org/10.3390/md17010005 - 21 Dec 2018
Cited by 15 | Viewed by 4301
Abstract
In this study, sulfated polysaccharide-rich extracts were isolated from 22 tropical seaweeds (4 red, 11 brown, and 7 green) found in northeastern Brazil, and evaluated for the role of anticoagulant agents. Fifteen of the extracts showed anticoagulant activity, including all the extracts from [...] Read more.
In this study, sulfated polysaccharide-rich extracts were isolated from 22 tropical seaweeds (4 red, 11 brown, and 7 green) found in northeastern Brazil, and evaluated for the role of anticoagulant agents. Fifteen of the extracts showed anticoagulant activity, including all the extracts from green seaweeds. Udotea flabellum (a green seaweed) extract was the most potent, requiring an amount of only 3 µg to double the plasma coagulation time in the activated partial thromboplastin time test. A similar result was obtained with 1 µg of heparin. Two sulfated homogalactans with anticoagulant activity, F-I (130 kDa) and F-II (75 kDa), were isolated from this extract using several bio-guided purification steps. Their anticoagulant activity, as well as properties related to antitumor activity (anti-proliferative, anti-adhesive, and anti-migratory), were accessed. Their anticoagulant activities were close to that of heparin. We found that F-I and F-II (0.5–10 μg/mL) were not able to directly inhibit thrombin. In the presence of anti-thrombin, F-I (0.5 μg/mL) was more effective than heparin (0.5 μg/mL) in inhibiting thrombin, while F-II showed similar effects as heparin. F-I and F-II also inhibited B16-F10 (murine melanoma cells) adhesion, migration, and proliferation on a fibronectin-coated surface, but not on laminin- or collagen I-coated surfaces. Except for the antiproliferative activity, the other effects of F-I and F-II were eliminated upon their desulfation (~50%), indicating that the degree of sulfation is not as important for F-I and F-II anti-proliferative activity as the sulfation position. Taken together, the results provide strong evidence for the potential utility of sulfated galactans from U. flabellum, making these compounds an interesting option for future investigations that aim to design new anticoagulant/antitumor agents. Full article
(This article belongs to the Special Issue Screening for Marine Natural Products with Potential as Chemotherapeutics)
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18 pages, 3086 KiB  
Article
A High-Content Screening Assay for the Discovery of Novel Proteasome Inhibitors from Formosan Soft Corals
by Xue-Hua Ling, Shang-Kwei Wang, Yun-Hsuan Huang, Min-Jay Huang and Chang-Yih Duh
Mar. Drugs 2018, 16(10), 395; https://doi.org/10.3390/md16100395 - 21 Oct 2018
Cited by 8 | Viewed by 3862
Abstract
The ubiquitin-proteasome system (UPS) is a major proteolytic pathway that safeguards protein homeostasis. The main 26S proteasome consists of a 20S catalytic core proteasome and a 19S substrate recognition proteasome. UPS dysfunction underlies many important clinical diseases involving inflammation, tumors, and neurodegeneration. Currently, [...] Read more.
The ubiquitin-proteasome system (UPS) is a major proteolytic pathway that safeguards protein homeostasis. The main 26S proteasome consists of a 20S catalytic core proteasome and a 19S substrate recognition proteasome. UPS dysfunction underlies many important clinical diseases involving inflammation, tumors, and neurodegeneration. Currently, three 20S proteasome inhibitors, bortezomib, carfilzomib, and ixazomib, have been approved for the treatment of multiple myeloma. We aim to screen UPS inhibitors for biomedical purposes. The protein interaction network of human cytomegalovirus UL76 targets UPS, resulting in aggregations of ubiquitinated proteins termed aggresomes. In this study, we demonstrated that cell-based high-content measurements of EGFP-UL76 aggresomes responded to bortezomib and MG132 treatment in a dose-dependent manner. Employing this high-content screening (HCS) assay, we screened natural compounds purified from Formosan soft corals. Four cembrane-based compounds, sarcophytonin A (1), sarcophytoxide (2), sarcophine (3), and laevigatol A (4), were found to enhance the high-content profiles of EGFP-UL76 aggresomes with relative ratios of 0.2. By comparison to the mechanistic action of proteasome inhibitors, compounds 1 and 3 modulated the accumulation of ubiquitinated proteins, with a unique pattern likely targeting 19S proteasome. We confirmed that the EGFP-UL76 aggresome-based HCS system greatly improves the efficacy and sensitivity of the identification of proteasome inhibitors. Full article
(This article belongs to the Special Issue Screening for Marine Natural Products with Potential as Chemotherapeutics)
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32 pages, 5604 KiB  
Article
Kororamides, Convolutamines, and Indole Derivatives as Possible Tau and Dual-Specificity Kinase Inhibitors for Alzheimer’s Disease: A Computational Study
by Laura Llorach-Pares, Alfons Nonell-Canals, Conxita Avila and Melchor Sanchez-Martinez
Mar. Drugs 2018, 16(10), 386; https://doi.org/10.3390/md16100386 - 16 Oct 2018
Cited by 29 | Viewed by 4726
Abstract
Alzheimer’s disease (AD) is becoming one of the most disturbing health and socioeconomic problems nowadays, as it is a neurodegenerative pathology with no treatment, which is expected to grow further due to population ageing. Actual treatments for AD produce only a modest amelioration [...] Read more.
Alzheimer’s disease (AD) is becoming one of the most disturbing health and socioeconomic problems nowadays, as it is a neurodegenerative pathology with no treatment, which is expected to grow further due to population ageing. Actual treatments for AD produce only a modest amelioration of symptoms, although there is a constant ongoing research of new therapeutic strategies oriented to improve the amelioration of the symptoms, and even to completely cure the disease. A principal feature of AD is the presence of neurofibrillary tangles (NFT) induced by the aberrant phosphorylation of the microtubule-associated protein tau in the brains of affected individuals. Glycogen synthetase kinase-3 beta (GSK3β), casein kinase 1 delta (CK1δ), dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) and dual-specificity kinase cdc2-like kinase 1 (CLK1) have been identified as the principal proteins involved in this process. Due to this, the inhibition of these kinases has been proposed as a plausible therapeutic strategy to fight AD. In this study, we tested in silico the inhibitory activity of different marine natural compounds, as well as newly-designed molecules from some of them, over the mentioned protein kinases, finding some new possible inhibitors with potential therapeutic application. Full article
(This article belongs to the Special Issue Screening for Marine Natural Products with Potential as Chemotherapeutics)
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