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Mar. Drugs, Volume 21, Issue 3 (March 2023) – 64 articles

Cover Story (view full-size image): The chemical space of polyarsenicals inspired by the arsenicin A–C metabolites from the New Caledonian sponge Echinochalina bargibanti has been enriched with synthetic dialkyl adamantane and thio-noradamantane analogs, including the identification of the scarce metabolite arsenicin D. Three arsenicin A-related compounds were selectively produced and evaluated for antitumor activity on glioblastoma stem cells (GSCs), a promising therapeutic target in glioblastoma treatment. These compounds inhibited the growth of nine GSC lines more potently than the FDA-approved anti-leukemic arsenic trioxide, with GI50 values in the submicromolar range, under both normoxic and hypoxic conditions, and presented high selectivity toward non-tumor cell lines. The diethyl and dipropyl analogs, which present favorable physicochemical and ADME predicted parameters, showed the most promising results. View this paper
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26 pages, 7845 KiB  
Article
Multiomic Approach for Bioprospection: Investigation of Toxins and Peptides of Brazilian Sea Anemone Bunodosoma caissarum
by Maria Eduarda Mazzi Esquinca, Claudia Neves Correa, Gabriel Marques de Barros, Horácio Montenegro and Leandro Mantovani de Castro
Mar. Drugs 2023, 21(3), 197; https://doi.org/10.3390/md21030197 - 22 Mar 2023
Cited by 4 | Viewed by 2131
Abstract
Sea anemones are sessile invertebrates of the phylum Cnidaria and their survival and evolutive success are highly related to the ability to produce and quickly inoculate venom, with the presence of potent toxins. In this study, a multi-omics approach was applied to characterize [...] Read more.
Sea anemones are sessile invertebrates of the phylum Cnidaria and their survival and evolutive success are highly related to the ability to produce and quickly inoculate venom, with the presence of potent toxins. In this study, a multi-omics approach was applied to characterize the protein composition of the tentacles and mucus of Bunodosoma caissarum, a species of sea anemone from the Brazilian coast. The tentacles transcriptome resulted in 23,444 annotated genes, of which 1% showed similarity with toxins or proteins related to toxin activity. In the proteome analysis, 430 polypeptides were consistently identified: 316 of them were more abundant in the tentacles while 114 were enriched in the mucus. Tentacle proteins were mostly enzymes, followed by DNA- and RNA-associated proteins, while in the mucus most proteins were toxins. In addition, peptidomics allowed the identification of large and small fragments of mature toxins, neuropeptides, and intracellular peptides. In conclusion, integrated omics identified previously unknown or uncharacterized genes in addition to 23 toxin-like proteins of therapeutic potential, improving the understanding of tentacle and mucus composition of sea anemones. Full article
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16 pages, 1993 KiB  
Article
Tetrodotoxin Decreases the Contractility of Mesenteric Arteries, Revealing the Contribution of Voltage-Gated Na+ Channels in Vascular Tone Regulation
by Joohee Park, Coralyne Proux, William Ehanno, Léa Réthoré, Emilie Vessières, Jennifer Bourreau, Julie Favre, Gilles Kauffenstein, César Mattei, Hélène Tricoire-Leignel, Daniel Henrion, Claire Legendre and Christian Legros
Mar. Drugs 2023, 21(3), 196; https://doi.org/10.3390/md21030196 - 22 Mar 2023
Viewed by 1597
Abstract
Tetrodotoxin (TTX) poisoning through the consumption of contaminated fish leads to lethal symptoms, including severe hypotension. This TTX-induced hypotension is likely due to the downfall of peripheral arterial resistance through direct or indirect effects on adrenergic signaling. TTX is a high-affinity blocker of [...] Read more.
Tetrodotoxin (TTX) poisoning through the consumption of contaminated fish leads to lethal symptoms, including severe hypotension. This TTX-induced hypotension is likely due to the downfall of peripheral arterial resistance through direct or indirect effects on adrenergic signaling. TTX is a high-affinity blocker of voltage-gated Na+ (NaV) channels. In arteries, NaV channels are expressed in sympathetic nerve endings, both in the intima and media. In this present work, we aimed to decipher the role of NaV channels in vascular tone using TTX. We first characterized the expression of NaV channels in the aorta, a model of conduction arteries, and in mesenteric arteries (MA), a model of resistance arteries, in C57Bl/6J mice, by Western blot, immunochemistry, and absolute RT-qPCR. Our data showed that these channels are expressed in both endothelium and media of aorta and MA, in which scn2a and scn1b were the most abundant transcripts, suggesting that murine vascular NaV channels consist of NaV1.2 channel subtype with NaVβ1 auxiliary subunit. Using myography, we showed that TTX (1 µM) induced complete vasorelaxation in MA in the presence of veratridine and cocktails of antagonists (prazosin and atropine with or without suramin) that suppressed the effects of neurotransmitter release. In addition, TTX (1 µM) strongly potentiated the flow-mediated dilation response of isolated MA. Altogether, our data showed that TTX blocks NaV channels in resistance arteries and consecutively decreases vascular tone. This could explain the drop in total peripheral resistance observed during mammal tetrodotoxications. Full article
(This article belongs to the Special Issue Tetrodotoxins: Detection, Biosynthesis and Biological Effects)
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11 pages, 3376 KiB  
Article
Antibacterial Indole Diketopiperazine Alkaloids from the Deep-Sea Cold Seep-Derived Fungus Aspergillus chevalieri
by Li-Hong Yan, Feng-Yu Du, Xiao-Ming Li, Sui-Qun Yang, Bin-Gui Wang and Xin Li
Mar. Drugs 2023, 21(3), 195; https://doi.org/10.3390/md21030195 - 22 Mar 2023
Cited by 5 | Viewed by 1838
Abstract
A large body of fungal secondary metabolites has been discovered to exhibit potent antibacterial activities with distinctive mechanisms and has the potential to be an untapped resource for drug discovery. Here, we describe the isolation and characterization of five new antibacterial indole diketopiperazine [...] Read more.
A large body of fungal secondary metabolites has been discovered to exhibit potent antibacterial activities with distinctive mechanisms and has the potential to be an untapped resource for drug discovery. Here, we describe the isolation and characterization of five new antibacterial indole diketopiperazine alkaloids, namely 24,25-dihydroxyvariecolorin G (1), 25-hydroxyrubrumazine B (2), 22-chloro-25-hydroxyrubrumazine B (3), 25-hydroxyvariecolorin F (4), and 27-epi-aspechinulin D (5), along with the known analogue neoechinulin B (6) from a fungal strain of deep-sea cold seep-derived Aspergillus chevalieri. Among these compounds, 3 and 4 represented a class of infrequently occurring fungal chlorinated natural products. Compounds 16 showed inhibitory activities against several pathogenic bacteria with MIC values ranging from 4 to 32 μg/mL. It was revealed that compound 6 could induce structural damage to the Aeromonas hydrophila cells based on the observation by scanning electron microscopy (SEM), which led to the bacteriolysis and death of A. hydrophila, suggesting that neoechinulin B (6) might be a potential alternative to novel antibiotics development. Full article
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21 pages, 1776 KiB  
Article
New Hybrid Phenalenone Dimer, Highly Conjugated Dihydroxylated C28 Steroid and Azaphilone from the Culture Extract of a Marine Sponge-Associated Fungus, Talaromyces pinophilus KUFA 1767
by Fátima P. Machado, Inês C. Rodrigues, Aikaterini Georgopolou, Luís Gales, José A. Pereira, Paulo M. Costa, Sharad Mistry, Salar Hafez Ghoran, Artur M. S. Silva, Tida Dethoup, Emília Sousa and Anake Kijjoa
Mar. Drugs 2023, 21(3), 194; https://doi.org/10.3390/md21030194 - 21 Mar 2023
Cited by 1 | Viewed by 1824
Abstract
An undescribed hybrid phenalenone dimer, talaropinophilone (3), an unreported azaphilone, 7-epi-pinazaphilone B (4), an unreported phthalide dimer, talaropinophilide (6), and an undescribed 9R,15S-dihydroxy-ergosta-4,6,8 (14)-tetraen-3-one (7) were isolated together with [...] Read more.
An undescribed hybrid phenalenone dimer, talaropinophilone (3), an unreported azaphilone, 7-epi-pinazaphilone B (4), an unreported phthalide dimer, talaropinophilide (6), and an undescribed 9R,15S-dihydroxy-ergosta-4,6,8 (14)-tetraen-3-one (7) were isolated together with the previously reported bacillisporins A (1) and B (2), an azaphilone derivative, Sch 1385568 (5), 1-deoxyrubralactone (8), acetylquestinol (9), piniterpenoid D (10) and 3,5-dihydroxy-4-methylphthalaldehydic acid (11) from the ethyl acetate extract of the culture of a marine sponge-derived fungus, Talaromyces pinophilus KUFA 1767. The structures of the undescribed compounds were elucidated by 1D and 2D NMR as well as high-resolution mass spectral analyses. The absolute configuration of C-9′ of 1 and 2 was revised to be 9′S using the coupling constant value between C-8′ and C-9′ and was confirmed by ROESY correlations in the case of 2. The absolute configurations of the stereogenic carbons in 7 and 8 were established by X-ray crystallographic analysis. Compounds 1,2, 48, 10 and 11 were tested for antibacterial activity against four reference strains, viz. two Gram-positive (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and two Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), as well as three multidrug-resistant strains, viz. an extended-spectrum β-lactamase (ESBL)-producing E. coli, a methicillin-resistant S. aureus (MRSA) and a vancomycin-resistant E. faecalis (VRE). However, only 1 and 2 exhibited significant antibacterial activity against both S. aureus ATCC 29213 and MRSA. Moreover, 1 and 2 also significantly inhibited biofilm formation in S. aureus ATCC 29213 at both MIC and 2xMIC concentrations. Full article
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29 pages, 2909 KiB  
Review
Marine-Derived Compounds Applied in Cardiovascular Diseases: Submerged Medicinal Industry
by Wasim Akram, Mohd Rihan, Sakeel Ahmed, Swamita Arora, Sameer Ahmad and Rahul Vashishth
Mar. Drugs 2023, 21(3), 193; https://doi.org/10.3390/md21030193 - 21 Mar 2023
Cited by 2 | Viewed by 3312
Abstract
Cardiovascular diseases (CVDs) are among the most impactful illnesses globally. Currently, the available therapeutic option has several side effects, including hypotension, bradycardia, arrhythmia, and alteration in different ion concentrations. Recently, bioactive compounds from natural sources, including plants, microorganisms, and marine creatures, have gained [...] Read more.
Cardiovascular diseases (CVDs) are among the most impactful illnesses globally. Currently, the available therapeutic option has several side effects, including hypotension, bradycardia, arrhythmia, and alteration in different ion concentrations. Recently, bioactive compounds from natural sources, including plants, microorganisms, and marine creatures, have gained a lot of interest. Marine sources serve as reservoirs for new bioactive metabolites with various pharmacological activities. The marine-derived compound such as omega-3 acid ethyl esters, xyloketal B, asperlin, and saringosterol showed promising results in several CVDs. The present review focuses on marine-derived compounds’ cardioprotective potential for hypertension, ischemic heart disease, myocardial infarction, and atherosclerosis. In addition to therapeutic alternatives, the current use of marine-derived components, the future trajectory, and restrictions are also reviewed. Full article
(This article belongs to the Special Issue Marine-Derived Compounds Applied in Cardiovascular Disease)
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17 pages, 3344 KiB  
Article
Recombinant Analogs of Sea Anemone Kunitz-Type Peptides Influence P2X7 Receptor Activity in Neuro-2a Cells
by Evgeny A. Pislyagin, Ekaterina S. Menchinskaya, Irina N. Gladkikh, Aleksandra N. Kvetkina, Oksana V. Sintsova, Darya V. Popkova, Sergei A. Kozlovskiy, Tatiana Y. Gorpenchenko, Galina N. Likhatskaya, Leonid A. Kaluzhskiy, Alexis S. Ivanov, Yaroslav A. Andreev, Sergey A. Kozlov, Pavel S. Dmitrenok, Dmitry L. Aminin and Elena V. Leychenko
Mar. Drugs 2023, 21(3), 192; https://doi.org/10.3390/md21030192 - 20 Mar 2023
Viewed by 1517
Abstract
Purinergic P2X7 receptors (P2X7) have now been proven to play an important role and represent an important therapeutic target in many pathological conditions including neurodegeneration. Here, we investigated the impact of peptides on purinergic signaling in Neuro-2a cells through the P2X7 subtype in [...] Read more.
Purinergic P2X7 receptors (P2X7) have now been proven to play an important role and represent an important therapeutic target in many pathological conditions including neurodegeneration. Here, we investigated the impact of peptides on purinergic signaling in Neuro-2a cells through the P2X7 subtype in in vitro models. We have found that a number of recombinant peptides, analogs of sea anemone Kunitz-type peptides, are able to influence the action of high concentrations of ATP and thereby reduce the toxic effects of ATP. The influx of calcium, as well as the fluorescent dye YO-PRO-1, was significantly suppressed by the studied peptides. Immunofluorescence experiments confirmed that the peptides reduce the P2X7 expression level in neuronal Neuro-2a cells. Two selected active peptides, HCRG1 and HCGS1.10, were found to specifically interact with the extracellular domain of P2X7 and formed stable complexes with the receptor in surface plasmon resonance experiments. The molecular docking approach allowed us to establish the putative binding sites of the most active HCRG1 peptide on the extracellular domain of the P2X7 homotrimer and propose a mechanism for regulating its function. Thus, our work demonstrates the ability of the Kunitz-type peptides to prevent neuronal death by affecting signaling through the P2X7 receptor. Full article
(This article belongs to the Special Issue Marine Drugs Research in Russia)
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13 pages, 1492 KiB  
Article
Semi-Synthesis and Biological Evaluation of 25(R)-26-Acetoxy-3β,5α-Dihydroxycholest-6-One
by Mireguli Maimaitiming, Ling Lv, Xuetao Zhang, Shuli Xia, Xin Li, Pingyuan Wang, Zhiqing Liu and Chang-Yun Wang
Mar. Drugs 2023, 21(3), 191; https://doi.org/10.3390/md21030191 - 20 Mar 2023
Viewed by 1724
Abstract
Previously, we identified a series of steroids (16) that showed potent anti-virus activities against respiratory syncytial virus (RSV), with IC50 values ranging from 3.23 to 0.19 µM. In this work, we first semi-synthesized and characterized the single isomer [...] Read more.
Previously, we identified a series of steroids (16) that showed potent anti-virus activities against respiratory syncytial virus (RSV), with IC50 values ranging from 3.23 to 0.19 µM. In this work, we first semi-synthesized and characterized the single isomer of 5, 25(R)-26-acetoxy-3β,5α-dihydroxycholest-6-one, named as (25R)-5, in seven steps from a commercially available compound diosgenin (7), with a total yield of 2.8%. Unfortunately, compound (25R)-5 and the intermediates only showed slight inhibitions against RSV replication at the concentration of 10 µM, but they possessed potent cytotoxicity activities against human bladder cancer 5637 (HTB-9) and hepatic cancer HepG2, with IC50 values ranging from 3.0 to 15.5 µM without any impression of normal liver cell proliferation at 20 µM. Among them, the target compound (25R)-5 possessed cytotoxicity activities against 5637 (HTB-9) and HepG2 with IC50 values of 4.8 µM and 15.5 µM, respectively. Further studies indicated that compound (25R)-5 inhibited cancer cell proliferation through inducing early and late-stage apoptosis. Collectively, we have semi-synthesized, characterized and biologically evaluated the 25R-isomer of compound 5; the biological results suggested that compound (25R)-5 could be a good lead for further anti-cancer studies, especially for anti-human liver cancer. Full article
(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)
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16 pages, 2920 KiB  
Article
Bioconversion of Cheese Whey and Food By-Products by Phaeodactylum tricornutum into Fucoxanthin and n-3 Lc-PUFA through a Biorefinery Approach
by Giovanni Luca Russo, Antonio Luca Langellotti, Vito Verardo, Beatriz Martín-García, Maria Oliviero, Marco Baselice, Prospero Di Pierro, Angela Sorrentino, Sharon Viscardi, Luis Marileo, Raffaele Sacchi and Paolo Masi
Mar. Drugs 2023, 21(3), 190; https://doi.org/10.3390/md21030190 - 19 Mar 2023
Cited by 3 | Viewed by 1835
Abstract
This study investigates the potential of utilizing three food wastes: cheese whey (CW), beet molasses (BM), and corn steep liquor (CSL) as alternative nutrient sources for the cultivation of the diatom Phaeodactylum tricornutum, a promising source of polyunsaturated eicosapentaenoic acid (EPA) and [...] Read more.
This study investigates the potential of utilizing three food wastes: cheese whey (CW), beet molasses (BM), and corn steep liquor (CSL) as alternative nutrient sources for the cultivation of the diatom Phaeodactylum tricornutum, a promising source of polyunsaturated eicosapentaenoic acid (EPA) and the carotenoid fucoxanthin. The CW media tested did not significantly impact the growth rate of P. tricornutum; however, CW hydrolysate significantly enhances cell growth. BM in cultivation medium enhances biomass production and fucoxanthin yield. The optimization of the new food waste medium was conducted through the application of a response surface methodology (RSM) using hydrolyzed CW, BM, and CSL as factors. The results showed a significant positive impact of these factors (p < 0.005), with an optimized biomass yield of 2.35 g L−1 and a fucoxanthin yield of 3.64 mg L−1 using a medium composed of 33 mL L−1 of CW, 2.3 g L−1 of BM, and 2.24 g L−1 of CSL. The experimental results reported in this study showed that some food by-products from a biorefinery perspective could be utilized for the efficient production of fucoxanthin and other high-added-value products such as eicosapentaenoic acid (EPA). Full article
(This article belongs to the Special Issue Biotechnology of Algae)
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17 pages, 5929 KiB  
Review
Alginate-Based Biomaterials in Tissue Engineering and Regenerative Medicine
by Nima Farshidfar, Siavash Iravani and Rajender S. Varma
Mar. Drugs 2023, 21(3), 189; https://doi.org/10.3390/md21030189 - 18 Mar 2023
Cited by 24 | Viewed by 3805
Abstract
Today, with the salient advancements of modern and smart technologies related to tissue engineering and regenerative medicine (TE-RM), the use of sustainable and biodegradable materials with biocompatibility and cost-effective advantages have been investigated more than before. Alginate as a naturally occurring anionic polymer [...] Read more.
Today, with the salient advancements of modern and smart technologies related to tissue engineering and regenerative medicine (TE-RM), the use of sustainable and biodegradable materials with biocompatibility and cost-effective advantages have been investigated more than before. Alginate as a naturally occurring anionic polymer can be obtained from brown seaweed to develop a wide variety of composites for TE, drug delivery, wound healing, and cancer therapy. This sustainable and renewable biomaterial displays several fascinating properties such as high biocompatibility, low toxicity, cost-effectiveness, and mild gelation by inserting divalent cations (e.g., Ca2+). In this context, challenges still exist in relation to the low solubility and high viscosity of high-molecular weight alginate, high density of intra- and inter-molecular hydrogen bonding, polyelectrolyte nature of the aqueous solution, and a lack of suitable organic solvents. Herein, TE-RM applications of alginate-based materials are deliberated, focusing on current trends, important challenges, and future prospects. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery 2nd Edition)
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17 pages, 745 KiB  
Article
Fatty Acids in Waste Tissues: The Nutraceutical Value of Gonads and Livers from the Moroccan Hypophthalmichthys molitrix and Cyprinus carpio Fishes
by Giuseppina Tommonaro, Debora Paris, Giulia Guerriero, Fatima-Zahra Majdoubi, Gaetano Grieco, Carmine Iodice, Lucio Caso, Anouar Ouizgane, Aziz El Moujtahid, Sara El Ghizi, Meriem Bousseba, Mustapha Hasnaoui, Annalaura Iodice and Annabella Tramice
Mar. Drugs 2023, 21(3), 188; https://doi.org/10.3390/md21030188 - 17 Mar 2023
Cited by 1 | Viewed by 1863
Abstract
Fishes are an important component of human nutrition, mainly acting as source of essential fatty acids in the prevention of cardiovascular disorders. The increase in their consumption has led to a growth of fishes waste; therefore, the disposal and recycling of waste has [...] Read more.
Fishes are an important component of human nutrition, mainly acting as source of essential fatty acids in the prevention of cardiovascular disorders. The increase in their consumption has led to a growth of fishes waste; therefore, the disposal and recycling of waste has become a key issue to address, in accordance with circular economy principles. The Moroccan Hypophthalmichthys molitrix and Cyprinus carpio fishes, living in freshwater and marine environments, were collected at mature and immature stages. The fatty acid (FA) profiles of liver and ovary tissues were investigated by GC–MS and compared with edible fillet tissues. The gonadosomatic index, the hypocholesterolemic/hypercholesterolemic ratio, and the atherogenicity and thrombogenicity indexes were measured. Polyunsaturated fatty acids were found to be abundant in the mature ovary and fillet of both species, with a polyunsaturated fatty acids/saturated fatty acids ratio ranging from 0.40 to 1.06 and a monounsaturated fatty acids/polyunsaturated fatty acids ratio between 0.64 and 1.84. Saturated fatty acids were found to be highly abundant in the liver and gonads of both species (range 30–54%), as well as monounsaturated fatty acids (range 35–58%). The results suggested that the exploitation of fish wastes, such as the liver and ovary, may represent a sustainable strategy for the achievement of high value-added molecules with nutraceutical potential. Full article
(This article belongs to the Special Issue Fatty Acids from Marine Organisms)
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20 pages, 11795 KiB  
Article
Fibrin and Marine-Derived Agaroses for the Generation of Human Bioartificial Tissues: An Ex Vivo and In Vivo Study
by Olimpia Ortiz-Arrabal, Ainhoa Irastorza-Lorenzo, Fernando Campos, Miguel Ángel Martín-Piedra, Víctor Carriel, Ingrid Garzón, Paula Ávila-Fernández, María José de Frutos, Emilio Esteban, Javier Fernández, Agustín Janer, Antonio Campos, Jesús Chato-Astrain and Miguel Alaminos
Mar. Drugs 2023, 21(3), 187; https://doi.org/10.3390/md21030187 - 17 Mar 2023
Cited by 5 | Viewed by 1309
Abstract
Development of an ideal biomaterial for clinical use is one of the main objectives of current research in tissue engineering. Marine-origin polysaccharides, in particular agaroses, have been widely explored as scaffolds for tissue engineering. We previously developed a biomaterial based on a combination [...] Read more.
Development of an ideal biomaterial for clinical use is one of the main objectives of current research in tissue engineering. Marine-origin polysaccharides, in particular agaroses, have been widely explored as scaffolds for tissue engineering. We previously developed a biomaterial based on a combination of agarose with fibrin, that was successfully translated to clinical practice. However, in search of novel biomaterials with improved physical and biological properties, we have now generated new fibrin-agarose (FA) biomaterials using 5 different types of agaroses at 4 different concentrations. First, we evaluated the cytotoxic effects and the biomechanical properties of these biomaterials. Then, each bioartificial tissue was grafted in vivo and histological, histochemical and immunohistochemical analyses were performed after 30 days. Ex vivo evaluation showed high biocompatibility and differences in their biomechanical properties. In vivo, FA tissues were biocompatible at the systemic and local levels, and histological analyses showed that biointegration was associated to a pro-regenerative process with M2-type CD206-positive macrophages. These results confirm the biocompatibility of FA biomaterials and support their clinical use for the generation of human tissues by tissue engineering, with the possibility of selecting specific agarose types and concentrations for applications requiring precise biomechanical properties and in vivo reabsorption times. Full article
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21 pages, 3702 KiB  
Article
Expanding the Chemical Space of Arsenicin A-C Related Polyarsenicals and Evaluation of Some Analogs as Inhibitors of Glioblastoma Stem Cell Growth
by Jacopo Vigna, Denise Sighel, Emanuele Filiberto Rosatti, Andrea Defant, Michael Pancher, Viktoryia Sidarovich, Alessandro Quattrone and Ines Mancini
Mar. Drugs 2023, 21(3), 186; https://doi.org/10.3390/md21030186 - 17 Mar 2023
Cited by 1 | Viewed by 1774
Abstract
The marine polyarsenical metabolite arsenicin A is the landmark of a series of natural and synthetic molecules characterized by an adamantane-like tetraarsenic cage. Arsenicin A and related polyarsenicals have been evaluated for their antitumor effects in vitro and have been proven more potent [...] Read more.
The marine polyarsenical metabolite arsenicin A is the landmark of a series of natural and synthetic molecules characterized by an adamantane-like tetraarsenic cage. Arsenicin A and related polyarsenicals have been evaluated for their antitumor effects in vitro and have been proven more potent than the FDA-approved arsenic trioxide. In this context, we have expanded the chemical space of polyarsenicals related to arsenicin A by synthesizing dialkyl and dimethyl thio-analogs, the latter characterized with the support of simulated NMR spectra. In addition, the new natural arsenicin D, the scarcity of which in the Echinochalina bargibanti extract had previously limited its full structural characterization, has been identified by synthesis. The dialkyl analogs, which present the adamantane-like arsenicin A cage substituted with either two methyl, ethyl, or propyl chains, were efficiently and selectively produced and evaluated for their activity on glioblastoma stem cells (GSCs), a promising therapeutic target in glioblastoma treatment. These compounds inhibited the growth of nine GSC lines more potently than arsenic trioxide, with GI50 values in the submicromolar range, both under normoxic and hypoxic conditions, and presented high selectivity toward non-tumor cell lines. The diethyl and dipropyl analogs, which present favorable physical-chemical and ADME parameters, had the most promising results. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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12 pages, 2473 KiB  
Article
Photochemical Reduction of Silver Nanoparticles on Diatoms
by Adrián León-Valencia, Sarah Briceño, Carlos Reinoso, Karla Vizuete, Alexis Debut, Manuel Caetano and Gema González
Mar. Drugs 2023, 21(3), 185; https://doi.org/10.3390/md21030185 - 17 Mar 2023
Viewed by 1775
Abstract
In this work, the photochemical reduction method was used at 440 or 540 nm excitation wavelengths to optimize the deposition of silver nanoparticles on the diatom surface as a potential DNA biosensor. The as-synthesized nanocomposites were characterized by ultraviolet-visible spectroscopy (UV-Vis), Fourier transforms [...] Read more.
In this work, the photochemical reduction method was used at 440 or 540 nm excitation wavelengths to optimize the deposition of silver nanoparticles on the diatom surface as a potential DNA biosensor. The as-synthesized nanocomposites were characterized by ultraviolet-visible spectroscopy (UV-Vis), Fourier transforms infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), scanning transmission electron microscopy (STEM), fluorescence microscopy, and Raman spectroscopy. Our results revealed a 5.5-fold enhancement in the fluorescence response of the nanocomposite irradiated at 440 nm with DNA. The enhanced sensitivity comes from the optical coupling of the guided-mode resonance of the diatoms and the localized surface plasmon of the silver nanoparticles interacting with the DNA. The advantage of this work involves the use of a low-cost green method to optimize the deposition of plasmonic nanoparticles on diatoms as an alternative fabrication method for fluorescent biosensors. Full article
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18 pages, 3409 KiB  
Article
A Distinct Saponin Profile Drives an Olfactory-Mediated Aggregation in the Aquacultivated Sea Cucumber Holothuria scabra
by Emily J. S. Claereboudt, Michel R. Claereboudt, Philippe Savarino, Guillaume Caulier, Loic Gaumez, Magali Deleu, Pascal Gerbaux and Igor Eeckhaut
Mar. Drugs 2023, 21(3), 184; https://doi.org/10.3390/md21030184 - 16 Mar 2023
Cited by 3 | Viewed by 1643
Abstract
Intraspecific chemical communication between echinoderms has often been limited to prespawning aggregation. However, sea cucumber farmers have long observed year-round adult aggregation as a potential source of disease propagation and the suboptimal use of available sea pen acreage and food resources. In this [...] Read more.
Intraspecific chemical communication between echinoderms has often been limited to prespawning aggregation. However, sea cucumber farmers have long observed year-round adult aggregation as a potential source of disease propagation and the suboptimal use of available sea pen acreage and food resources. In this study, through spatial distribution statistics, we demonstrated the significant aggregation of the aquacultivated sea cucumber Holothuria scabra both as adults in large sea-based pens and as juveniles in laboratory-based aquaria, proving that aggregation in these animals is not only observed during spawning. The role of chemical communication in aggregation was investigated using olfactory experimental assays. Our study established that the sediment that H. scabra feeds on as well as the water preconditioned by conspecifics induced positive chemotaxis in juvenile individuals. More specifically, through comparative mass spectrometry, a distinct triterpenoid saponin profile/mixture was identified to be a pheromone allowing sea cucumber intraspecific recognition and aggregation. This “attractive” profile was characterized as containing disaccharide saponins. This “attractive” aggregation-inducing saponin profile was, however, not conserved in starved individuals that were no longer attractive to other conspecifics. In summary, this study sheds new light on the pheromones in echinoderms. It highlights the complexity of the chemical signals detected by sea cucumbers and suggests a role of saponins well beyond that of a simple toxin. Full article
(This article belongs to the Section Marine Chemoecology for Drug Discovery)
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15 pages, 1877 KiB  
Article
Water-Soluble Saccharina latissima Polysaccharides and Relation of Their Structural Characteristics with In Vitro Immunostimulatory and Hypocholesterolemic Activities
by Ana S. P. Moreira, Diana Gaspar, Sónia S. Ferreira, Alexandra Correia, Manuel Vilanova, Marie-Mathilde Perrineau, Philip D. Kerrison, Claire M. M. Gachon, Maria Rosário Domingues, Manuel A. Coimbra, Filipe M. Coreta-Gomes and Cláudia Nunes
Mar. Drugs 2023, 21(3), 183; https://doi.org/10.3390/md21030183 - 16 Mar 2023
Cited by 7 | Viewed by 2070
Abstract
Brown macroalgae are an important source of polysaccharides, mainly fucose-containing sulphated polysaccharides (FCSPs), associated with several biological activities. However, the structural diversity and structure–function relationships for their bioactivities are still undisclosed. Thus, the aim of this work was to characterize the chemical structure [...] Read more.
Brown macroalgae are an important source of polysaccharides, mainly fucose-containing sulphated polysaccharides (FCSPs), associated with several biological activities. However, the structural diversity and structure–function relationships for their bioactivities are still undisclosed. Thus, the aim of this work was to characterize the chemical structure of water-soluble Saccharina latissima polysaccharides and evaluate their immunostimulatory and hypocholesterolemic activities, helping to pinpoint a structure–activity relationship. Alginate, laminarans (F1, neutral glucose-rich polysaccharides), and two fractions (F2 and F3) of FCSPs (negatively charged) were studied. Whereas F2 is rich in uronic acids (45 mol%) and fucose (29 mol%), F3 is rich in fucose (59 mol%) and galactose (21 mol%). These two fractions of FCSPs showed immunostimulatory activity on B lymphocytes, which could be associated with the presence of sulphate groups. Only F2 exhibited a significant effect in reductions in in vitro cholesterol’s bioaccessibility attributed to the sequestration of bile salts. Therefore, S. latissima FCSPs were shown to have potential as immunostimulatory and hypocholesterolemic functional ingredients, where their content in uronic acids and sulphation seem to be relevant for the bioactive and healthy properties. Full article
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34 pages, 11369 KiB  
Review
Pro-Apoptotic Activity of Bioactive Compounds from Seaweeds: Promising Sources for Developing Novel Anticancer Drugs
by Rosette Agena, Alejandro de Jesús Cortés-Sánchez, Humberto Hernández-Sánchez and María Eugenia Jaramillo-Flores
Mar. Drugs 2023, 21(3), 182; https://doi.org/10.3390/md21030182 - 15 Mar 2023
Cited by 7 | Viewed by 2432
Abstract
The process by which cancer cells evade or inhibit apoptosis is considered one of the characteristics of cancer. The ability of cancer cells to escape apoptosis contributes to tumor proliferation and promotes metastasis. The discovery of new antitumor agents is essential for cancer [...] Read more.
The process by which cancer cells evade or inhibit apoptosis is considered one of the characteristics of cancer. The ability of cancer cells to escape apoptosis contributes to tumor proliferation and promotes metastasis. The discovery of new antitumor agents is essential for cancer treatment due to the lack of selectivity of drugs and cellular resistance to anticancer agents. Several studies showed that macroalgae produce various metabolites with different biological activities among marine organisms. This review discusses multiple metabolites extracted from macroalgae and their pro-apoptotic effects through regulating apoptosis signaling pathway target molecules and the structure-activity relationship. Twenty-four promising bioactive compounds have been reported, where eight of these compounds exhibited values of maximum inhibitory concentration (IC50) of less than 7 μg/mL. Fucoxanthin was the only carotenoid reported that induced apoptosis in HeLa cells with an IC50 below 1 µg/mL. Se-PPC (a complex of proteins and selenylated polysaccharides) is the magistral compound because it is the only one with an IC50 of 2.5 µg/mL which regulates the primary proteins and critical genes of both apoptosis pathways. Therefore, this review will help provide the basis for further studies and the development of new anticancer drugs, both as single agents and adjuvants, decreasing the aggressiveness of first-line drugs and offering patients better survival and quality of life. Full article
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10 pages, 542 KiB  
Article
Antioxidative Indenone and Benzophenone Derivatives from the Mangrove-Derived Fungus Cytospora heveae NSHSJ-2
by Ge Zou, Taobo Li, Wencong Yang, Bing Sun, Yan Chen, Bo Wang, Yanghui Ou, Huijuan Yu and Zhigang She
Mar. Drugs 2023, 21(3), 181; https://doi.org/10.3390/md21030181 - 14 Mar 2023
Cited by 3 | Viewed by 1438
Abstract
Seven new polyketides, including four indenone derivatives, cytoindenones A–C (1, 34), 3′-methoxycytoindenone A (2), a benzophenone derivative, cytorhizophin J (6), and a pair of tetralone enantiomers, (±)-4,6-dihydroxy-5-methoxy-α-tetralone (7), together with [...] Read more.
Seven new polyketides, including four indenone derivatives, cytoindenones A–C (1, 34), 3′-methoxycytoindenone A (2), a benzophenone derivative, cytorhizophin J (6), and a pair of tetralone enantiomers, (±)-4,6-dihydroxy-5-methoxy-α-tetralone (7), together with a known compound (5) were obtained from the endophytic fungus Cytospora heveae NSHSJ-2 isolated from the fresh stem of the mangrove plant Sonneratia caseolaris. Compound 3 represented the first natural indenone monomer substituted by two benzene moieties at C-2 and C-3. Their structures were determined by the analysis of 1D and 2D NMR, as well as mass spectroscopic data, and the absolute configurations of (±)-7 were determined on the basis of the observed specific rotation value compared with those of the tetralone derivatives previously reported. In bioactivity assays, compounds 1, 46 showed potent DPPH· scavenging activities, with EC50 values ranging from 9.5 to 16.6 µM, better than the positive control ascorbic acid (21.9 µM); compounds 23 also exhibited DPPH· scavenging activities comparable to ascorbic acid. Full article
(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)
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14 pages, 11714 KiB  
Article
Efficient Degradation of Alginate and Preparation of Alginate Oligosaccharides by a Novel Biofunctional Alginate Lyase with High Activity and Excellent Thermophilic Features
by Li Li, Shengsheng Cao, Benwei Zhu, Zhong Yao, Bo Zhu, Yimin Qin and Jinju Jiang
Mar. Drugs 2023, 21(3), 180; https://doi.org/10.3390/md21030180 - 14 Mar 2023
Cited by 3 | Viewed by 1428
Abstract
The enzymatic degradation of seaweed polysaccharides is gaining interest for its potential in the production of functional oligosaccharides and fermentable sugars. Herein, a novel alginate lyase, AlyRm3, was cloned from a marine strain, Rhodothermus marinus DSM 4252. The AlyRm3 showed optimal activity (37,315.08 [...] Read more.
The enzymatic degradation of seaweed polysaccharides is gaining interest for its potential in the production of functional oligosaccharides and fermentable sugars. Herein, a novel alginate lyase, AlyRm3, was cloned from a marine strain, Rhodothermus marinus DSM 4252. The AlyRm3 showed optimal activity (37,315.08 U/mg) at 70 °C and pH 8.0, with the sodium alginate used as a substrate. Noticeably, AlyRm3 was stable at 65 °C and also exhibited 30% of maximal activity at 90 °C. These results indicated that AlyRm3 is a thermophilic alginate lyase that efficiently degrades alginate at high industrial temperatures (>60 °C). The FPLC and ESI−MS analyses suggested that AlyRm3 primarily released disaccharides and trisaccharides from the alginate, polyM, and polyG in an endolytic manner. In the saccharification process of sodium alginate (0.5%, w/v), the AlyRm3 yielded numerous reducing sugars (1.73 g/L) after 2 h of reaction. These results indicated that AlyRm3 has a high enzymatic capacity for saccharifying the alginate, and could be used to saccharify the alginate biomass before the main fermentation process for biofuels. These properties make AlyRm3 a valuable candidate for both fundamental research and industrial applications. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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18 pages, 2451 KiB  
Article
Chitosan/Albumin Coating Factorial Optimization of Alginate/Dextran Sulfate Cores for Oral Delivery of Insulin
by Bruno Pessoa, Mar Collado-Gonzalez, Giuseppina Sandri and António Ribeiro
Mar. Drugs 2023, 21(3), 179; https://doi.org/10.3390/md21030179 - 14 Mar 2023
Cited by 2 | Viewed by 1580
Abstract
The design of nanoparticle formulations composed of biopolymers, that govern the physicochemical properties of orally delivered insulin, relies on improving insulin stability and absorption through the intestinal mucosa while protecting it from harsh conditions in the gastrointestinal (GI) tract. Chitosan/polyethylene glycol (PEG) and [...] Read more.
The design of nanoparticle formulations composed of biopolymers, that govern the physicochemical properties of orally delivered insulin, relies on improving insulin stability and absorption through the intestinal mucosa while protecting it from harsh conditions in the gastrointestinal (GI) tract. Chitosan/polyethylene glycol (PEG) and albumin coating of alginate/dextran sulfate hydrogel cores are presented as a multilayer complex protecting insulin within the nanoparticle. This study aims to optimize a nanoparticle formulation by assessing the relationship between design parameters and experimental data using response surface methodology through a 3-factor 3-level optimization Box–Behnken design. While the selected independent variables were the concentrations of PEG, chitosan and albumin, the dependent variables were particle size, polydispersity index (PDI), zeta potential, and insulin release. Experimental results showed a nanoparticle size ranging from 313 to 585 nm, with PDI from 0.17 to 0.39 and zeta potential ranging from −29 to −44 mV. Insulin bioactivity was maintained in simulated GI media with over 45% cumulative release after 180 min in a simulated intestinal medium. Based on the experimental responses and according to the criteria of desirability on the experimental region’s constraints, solutions of 0.03% PEG, 0.047% chitosan and 1.20% albumin provide an optimum nanoparticle formulation for insulin oral delivery. Full article
(This article belongs to the Special Issue Marine Biopolymers and Their Applications in Drug Delivery)
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17 pages, 4042 KiB  
Article
New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus Penicillium antarcticum KMM 4685
by Elena V. Leshchenko, Alexandr S. Antonov, Gleb V. Borkunov, Jessica Hauschild, Olesya I. Zhuravleva, Yuliya V. Khudyakova, Alexander S. Menshov, Roman S. Popov, Natalya Yu Kim, Markus Graefen, Carsten Bokemeyer, Gunhild von Amsberg, Anton N. Yurchenko and Sergey A. Dyshlovoy
Mar. Drugs 2023, 21(3), 178; https://doi.org/10.3390/md21030178 - 14 Mar 2023
Cited by 2 | Viewed by 1871
Abstract
Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (1), β-resoantarctines A-C (3, 5, 6) and 8-dehydro-β-resoantarctine A (4), together with known 14-hydroxyasperentin (5′-hydroxyasperentin) (2), were isolated from the ethyl acetate extract of the fungus [...] Read more.
Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (1), β-resoantarctines A-C (3, 5, 6) and 8-dehydro-β-resoantarctine A (4), together with known 14-hydroxyasperentin (5′-hydroxyasperentin) (2), were isolated from the ethyl acetate extract of the fungus Penicillium antarcticum KMM 4685 associated with the brown alga Sargassum miyabei. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher’s method, and the biogenetic pathways for compounds 36 were proposed. For the very first time, the relative configuration of the C-14 center of a known compound 2 was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites 36 were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds 3, 4 and 5 exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells. Full article
(This article belongs to the Special Issue Marine Drugs Research in Russia)
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24 pages, 2598 KiB  
Review
Alginate-Based Hydrogels and Scaffolds for Biomedical Applications
by Simonida Lj. Tomić, Marija M. Babić Radić, Jovana S. Vuković, Vuk V. Filipović, Jasmina Nikodinovic-Runic and Marija Vukomanović
Mar. Drugs 2023, 21(3), 177; https://doi.org/10.3390/md21030177 - 13 Mar 2023
Cited by 13 | Viewed by 3430
Abstract
Alginate is a natural polymer of marine origin and, due to its exceptional properties, has great importance as an essential component for the preparation of hydrogels and scaffolds for biomedical applications. The design of biologically interactive hydrogels and scaffolds with advanced, expected and [...] Read more.
Alginate is a natural polymer of marine origin and, due to its exceptional properties, has great importance as an essential component for the preparation of hydrogels and scaffolds for biomedical applications. The design of biologically interactive hydrogels and scaffolds with advanced, expected and required properties are one of the key issues for successful outcomes in the healing of injured tissues. This review paper presents the multifunctional biomedical applications of alginate-based hydrogels and scaffolds in selected areas, highlighting the key effect of alginate and its influence on the essential properties of the selected biomedical applications. The first part covers scientific achievements for alginate in dermal tissue regeneration, drug delivery systems, cancer treatment, and antimicrobials. The second part is dedicated to our scientific results obtained for the research opus of hydrogel materials for scaffolds based on alginate in synergy with different materials (polymers and bioactive agents). Alginate has proved to be an exceptional polymer for combining with other naturally occurring and synthetic polymers, as well as loading bioactive therapeutic agents to achieve dermal, controlled drug delivery, cancer treatment, and antimicrobial purposes. Our research was based on combinations of alginate with gelatin, 2-hydroxyethyl methacrylate, apatite, graphene oxide and iron(III) oxide, as well as curcumin and resveratrol as bioactive agents. Important features of the prepared scaffolds, such as morphology, porosity, absorption capacity, hydrophilicity, mechanical properties, in vitro degradation, and in vitro and in vivo biocompatibility, have shown favorable properties for the aforementioned applications, and alginate has been an important link in achieving these properties. Alginate, as a component of these systems, proved to be an indispensable factor and played an excellent “role” in the optimal adjustment of the tested properties. This study provides valuable data and information for researchers and demonstrates the importance of the role of alginate as a biomaterial in the design of hydrogels and scaffolds that are powerful medical “tools” for biomedical applications. Full article
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23 pages, 6419 KiB  
Review
Astaxanthin as a King of Ketocarotenoids: Structure, Synthesis, Accumulation, Bioavailability and Antioxidant Properties
by Anagha Nair, Ankesh Ahirwar, Shashikala Singh, Reeta Lodhi, Aishwarya Lodhi, Anshuman Rai, Dipak A Jadhav, Harish, Sunita Varjani, Gurpreet Singh, Justine Marchand, Benoît Schoefs and Vandana Vinayak
Mar. Drugs 2023, 21(3), 176; https://doi.org/10.3390/md21030176 - 13 Mar 2023
Cited by 15 | Viewed by 4420
Abstract
Astaxanthin (3,3-dihydroxy-β, β-carotene-4,4-dione) is a ketocarotenoid synthesized by Haematococcus pluvialis/lacustris, Chromochloris zofingiensis, Chlorococcum, Bracteacoccus aggregatus, Coelastrella rubescence, Phaffia rhodozyma, some bacteria (Paracoccus carotinifaciens), yeasts, and lobsters, among others However, it is majorly synthesized by Haematococcus [...] Read more.
Astaxanthin (3,3-dihydroxy-β, β-carotene-4,4-dione) is a ketocarotenoid synthesized by Haematococcus pluvialis/lacustris, Chromochloris zofingiensis, Chlorococcum, Bracteacoccus aggregatus, Coelastrella rubescence, Phaffia rhodozyma, some bacteria (Paracoccus carotinifaciens), yeasts, and lobsters, among others However, it is majorly synthesized by Haematococcus lacustris alone (about 4%). The richness of natural astaxanthin over synthetic astaxanthin has drawn the attention of industrialists to cultivate and extract it via two stage cultivation process. However, the cultivation in photobioreactors is expensive, and converting it in soluble form so that it can be easily assimilated by our digestive system requires downstream processing techniques which are not cost-effective. This has made the cost of astaxanthin expensive, prompting pharmaceutical and nutraceutical companies to switch over to synthetic astaxanthin. This review discusses the chemical character of astaxanthin, more inexpensive cultivating techniques, and its bioavailability. Additionally, the antioxidant character of this microalgal product against many diseases is discussed, which can make this natural compound an excellent drug to minimize inflammation and its consequences. Full article
(This article belongs to the Special Issue Microalgal Carotenoids)
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10 pages, 2761 KiB  
Article
Effect of Storage Time and Temperature on the Bioactivity of a Chitosan-Derived Epigenetic Modulation Scaffold
by Teerawat Sukpaita, Suwabun Chirachanchai, Atiphan Pimkhaokham and Ruchanee Salingcarnboriboon Ampornaramveth
Mar. Drugs 2023, 21(3), 175; https://doi.org/10.3390/md21030175 - 12 Mar 2023
Cited by 2 | Viewed by 1383
Abstract
The appropriate storage protocol is one of the main limitations of translating tissue engineering technology to commercialized clinical applications. Recently, the development of a chitosan-derived composite scaffold incorporated with bioactive molecules has been reported as an excellent material to repair a critical size [...] Read more.
The appropriate storage protocol is one of the main limitations of translating tissue engineering technology to commercialized clinical applications. Recently, the development of a chitosan-derived composite scaffold incorporated with bioactive molecules has been reported as an excellent material to repair a critical size bony defect in mice calvaria. This study aims to determine the storage time and appropriate storage temperature of Chitosan/Biphasic Calcium Phosphate/Trichostatin A composite scaffold (CS/BCP/TSA scaffold) in vitro. The mechanical properties and in vitro bioactivity of trichostatin A (TSA) released from CS/BCP/TSA scaffolds in different storage times and temperatures were evaluated. Different storage times (0, 14, and 28 days) and temperatures (−18, 4, and 25 °C) did not affect the porosity, compressive strength, shape memory, and amount of TSA released. However, scaffolds stored at 25 °C and 4 °C were found to lose their bioactivity after 3- and 7-day storage periods, respectively. Thus, the CS/BCP/TSA scaffold should be stored in freezing conditions to preserve the long-term stability of TSA. Full article
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39 pages, 3219 KiB  
Review
Impact of Marine Chemical Ecology Research on the Discovery and Development of New Pharmaceuticals
by Lik Tong Tan
Mar. Drugs 2023, 21(3), 174; https://doi.org/10.3390/md21030174 - 09 Mar 2023
Cited by 8 | Viewed by 5410
Abstract
Diverse ecologically important metabolites, such as allelochemicals, infochemicals and volatile organic chemicals, are involved in marine organismal interactions. Chemically mediated interactions between intra- and interspecific organisms can have a significant impact on community organization, population structure and ecosystem functioning. Advances in analytical techniques, [...] Read more.
Diverse ecologically important metabolites, such as allelochemicals, infochemicals and volatile organic chemicals, are involved in marine organismal interactions. Chemically mediated interactions between intra- and interspecific organisms can have a significant impact on community organization, population structure and ecosystem functioning. Advances in analytical techniques, microscopy and genomics are providing insights on the chemistry and functional roles of the metabolites involved in such interactions. This review highlights the targeted translational value of several marine chemical ecology-driven research studies and their impact on the sustainable discovery of novel therapeutic agents. These chemical ecology-based approaches include activated defense, allelochemicals arising from organismal interactions, spatio-temporal variations of allelochemicals and phylogeny-based approaches. In addition, innovative analytical techniques used in the mapping of surface metabolites as well as in metabolite translocation within marine holobionts are summarized. Chemical information related to the maintenance of the marine symbioses and biosyntheses of specialized compounds can be harnessed for biomedical applications, particularly in microbial fermentation and compound production. Furthermore, the impact of climate change on the chemical ecology of marine organisms—especially on the production, functionality and perception of allelochemicals—and its implications on drug discovery efforts will be presented. Full article
(This article belongs to the Section Marine Chemoecology for Drug Discovery)
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14 pages, 1227 KiB  
Article
Swim Bladder of Farmed Totoaba macdonaldi: A Source of Value-Added Collagen
by Honorio Cruz-López, Sergio Rodríguez-Morales, Luis M. Enríquez-Paredes, Luis Jesús Villarreal-Gómez, Conal True, Leticia Olivera-Castillo, D. Alejandro Fernández-Velasco and Lus M. López
Mar. Drugs 2023, 21(3), 173; https://doi.org/10.3390/md21030173 - 09 Mar 2023
Cited by 6 | Viewed by 1719
Abstract
Finding strategies to use the swim bladder of farmed totoaba (Totoaba macdonaldi) is of the utmost need to reduce waste. Fish swim bladders are rich in collagen; hence, extracting collagen is a promising alternative with benefits for aquaculture of totoaba and [...] Read more.
Finding strategies to use the swim bladder of farmed totoaba (Totoaba macdonaldi) is of the utmost need to reduce waste. Fish swim bladders are rich in collagen; hence, extracting collagen is a promising alternative with benefits for aquaculture of totoaba and the environment. The elemental biochemical composition of totoaba swim bladders, including their proximate and amino acid compositions, was determined. Pepsin-soluble collagen (PSC) was used to extract collagen from swim bladders, and its characteristics were analyzed. Alcalase and papain were used for the preparation of collagen hydrolysates. Swim bladders contained 95% protein, 2.4% fat, and 0.8% ash (on a dry basis). The essential amino acid content was low, but the functional amino acid content was high. The PSC yield was high, at 68% (dry weight). The amino acid composition profile, electrophoretic pattern, and structural integrity analyses of the isolated collagen suggested it is a typical type-I collagen with high purity. The denaturalization temperature was 32.5 °C, probably attributable to the imino acid content (205 residues/1000 residues). Papain-hydrolysates (≤3 kDa) of this collagen exhibited higher radical scavenging activity than Alcalase-hydrolysates. The swim bladder from the farmed totoaba could be an ideal source to produce high-quality type I collagen and may be considered an alternative to conventional collagen sources or bioactive peptides. Full article
(This article belongs to the Special Issue Collagen and Bioactives from Marine By-Products)
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32 pages, 761 KiB  
Review
Applications of Antioxidant Secondary Metabolites of Sargassum spp.
by Marcelo D. Catarino, Rita Silva-Reis, Amina Chouh, Sónia Silva, Susana S. Braga, Artur M. S. Silva and Susana M. Cardoso
Mar. Drugs 2023, 21(3), 172; https://doi.org/10.3390/md21030172 - 09 Mar 2023
Cited by 8 | Viewed by 6145
Abstract
Sargassum is one of the largest and most diverse genus of brown seaweeds, comprising of around 400 taxonomically accepted species. Many species of this genus have long been a part of human culture with applications as food, feed, and remedies in folk medicine. [...] Read more.
Sargassum is one of the largest and most diverse genus of brown seaweeds, comprising of around 400 taxonomically accepted species. Many species of this genus have long been a part of human culture with applications as food, feed, and remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of natural antioxidant compounds of great interest, including polyphenols, carotenoids, meroterpenoids, phytosterols, and several others. Such compounds provide a valuable contribution to innovation that can translate, for instance, into the development of new ingredients for preventing product deterioration, particularly in food products, cosmetics or biostimulants to boost crops production and tolerance to abiotic stress. This manuscript revises the chemical composition of Sargassum seaweeds, highlighting their antioxidant secondary metabolites, their mechanism of action, and multiple applications in fields, including agriculture, food, and health. Full article
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12 pages, 5654 KiB  
Article
New Data on the Rhamnose-Binding Lectin from the Colonial Ascidian Botryllus schlosseri: Subcellular Distribution, Secretion Mode and Effects on the Cyclical Generation Change
by Giacomo Bovo and Loriano Ballarin
Mar. Drugs 2023, 21(3), 171; https://doi.org/10.3390/md21030171 - 08 Mar 2023
Cited by 1 | Viewed by 1454
Abstract
Botryllus schlosseri in a cosmopolitan ascidian, considered a reliable model organism for studies on the evolution of the immune system. B. schlosseri rhamnose-binding lectin (BsRBL) is synthesised by circulating phagocytes and behaves as an opsonin by interacting with foreign cells or particles and [...] Read more.
Botryllus schlosseri in a cosmopolitan ascidian, considered a reliable model organism for studies on the evolution of the immune system. B. schlosseri rhamnose-binding lectin (BsRBL) is synthesised by circulating phagocytes and behaves as an opsonin by interacting with foreign cells or particles and acting as a molecular bridge between them and the phagocyte surface. Although described in previous works, many aspects and roles of this lectin in Botryllus biology remain unknown. Here, we studied the subcellular distribution of BsRBL during immune responses using light and electron microscopy. In addition, following the hints from extant data, suggesting a possible role of BsRBL in the process of cyclical generation change or takeover, we investigated the effects of interfering with this protein, by injecting a specific antibody in the colonial circulation, starting one day before the generation change. Results confirm the requirement of the lectin for a correct generation change and open new queries on the roles of this lectin in Botryllus biology. Full article
(This article belongs to the Special Issue Marine Glycomics 2nd Edition)
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23 pages, 1620 KiB  
Review
Marine Natural Products as Innovative Cosmetic Ingredients
by Sara Fonseca, Mariana Neves Amaral, Catarina Pinto Reis and Luísa Custódio
Mar. Drugs 2023, 21(3), 170; https://doi.org/10.3390/md21030170 - 08 Mar 2023
Cited by 17 | Viewed by 5993
Abstract
Over the course of the last 20 years, numerous studies have identified the benefits of an array of marine natural ingredients for cosmetic purposes, as they present unique characteristics not found in terrestrial organisms. Consequently, several marine-based ingredients and bioactive compounds are under [...] Read more.
Over the course of the last 20 years, numerous studies have identified the benefits of an array of marine natural ingredients for cosmetic purposes, as they present unique characteristics not found in terrestrial organisms. Consequently, several marine-based ingredients and bioactive compounds are under development, used or considered for skin care and cosmetics. Despite the multitude of cosmetics based on marine sources, only a small proportion of their full potential has been exploited. Many cosmetic industries have turned their attention to the sea to obtain innovative marine-derived compounds for cosmetics, but further research is needed to determine and elucidate the benefits. This review gathers information on the main biological targets for cosmetic ingredients, different classes of marine natural products of interest for cosmetic applications, and the organisms from which such products can be sourced. Although organisms from different phyla present different and varied bioactivities, the algae phylum seems to be the most promising for cosmetic applications, presenting compounds of many classes. In fact, some of these compounds present higher bioactivities than their commercialized counterparts, demonstrating the potential presented by marine-derived compounds for cosmetic applications (i.e., Mycosporine-like amino acids and terpenoids’ antioxidant activity). This review also summarizes the major challenges and opportunities faced by marine-derived cosmetic ingredients to successfully reach the market. As a future perspective, we consider that fruitful cooperation among academics and cosmetic industries could lead to a more sustainable market through responsible sourcing of ingredients, implementing ecological manufacturing processes, and experimenting with inventive recycling and reuse programs. Full article
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24 pages, 4475 KiB  
Article
Eighteen Novel Bioactive Peptides from Monkfish (Lophius litulon) Swim Bladders: Production, Identification, Antioxidant Activity, and Stability
by Yan Sheng, Wan-Yi Wang, Ming-Feng Wu, Yu-Mei Wang, Wang-Yu Zhu, Chang-Feng Chi and Bin Wang
Mar. Drugs 2023, 21(3), 169; https://doi.org/10.3390/md21030169 - 07 Mar 2023
Cited by 44 | Viewed by 2257
Abstract
In the study, papain was chosen from five proteases to hydrolyze proteins of monkfish swim bladders for effectively utilizing monkfish (Lophius litulon) processing byproducts, and the hydrolysis conditions of papain were optimized as hydrolysis temperature of 65 °C, pH 7.5, enzyme [...] Read more.
In the study, papain was chosen from five proteases to hydrolyze proteins of monkfish swim bladders for effectively utilizing monkfish (Lophius litulon) processing byproducts, and the hydrolysis conditions of papain were optimized as hydrolysis temperature of 65 °C, pH 7.5, enzyme dose 2.5% and time 5 h using single-factor and orthogonal experiments. Eighteen peptides were purified from the swim bladder hydrolysate of monkfish by ultrafiltration and gel permeation chromatography methods and identified as YDYD, QDYD, AGPAS, GPGPHGPSGP, GPK, HRE, GRW, ARW, GPTE, DDGGK, IGPAS, AKPAT, YPAGP, DPT, FPGPT, GPGPT, GPT and DPAGP, respectively. Among eighteen peptides, GRW and ARW showed significant DPPH· scavenging activities with EC50 values of 1.053 ± 0.003 and 0.773 ± 0.003 mg/mL, respectively; YDYD, QDYD, GRW, ARW and YPAGP revealed significantly HO· scavenging activities with EC50 values of 0.150 ± 0.060, 0.177 ± 0.035, 0.201 ± 0.013, 0.183 ± 0.0016 and 0.190 ± 0.010 mg/mL, respectively; YDYD, QDYD, ARW, DDGGK and YPAGP have significantly O2· scavenging capability with EC50 values of 0.126 ± 0.0005, 0.112 ± 0.0028, 0.127 ± 0.0002, 0.128 ± 0.0018 and 0.107 ± 0.0002 mg/mL, respectively; and YDYD, QDYD and YPAGP showed strong ABTS+· scavenging ability with EC50 values of 3.197 ± 0.036, 2.337 ± 0.016 and 3.839 ± 0.102 mg/mL, respectively. YDYD, ARW and DDGGK displayed the remarkable ability of lipid peroxidation inhibition and Ferric-reducing antioxidant properties. Moreover, YDYD and ARW can protect Plasmid DNA and HepG2 cells against H2O2-induced oxidative stress. Furthermore, eighteen isolated peptides had high stability under temperatures ranging from 25–100 °C; YDYD, QDYD, GRW and ARW were more sensitive to alkali treatment, but DDGGK and YPAGP were more sensitive to acid treatment; and YDYD showed strong stability treated with simulated GI digestion. Therefore, the prepared antioxidant peptides, especially YDYD, QDYD, GRW, ARW, DDGGK and YPAGP from monkfish swim bladders could serve as functional components applied in health-promoting products because of their high-antioxidant functions. Full article
(This article belongs to the Special Issue Marine Bioactive Peptides—Structure, Function, and Application)
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33 pages, 7121 KiB  
Article
Chemical Compositions and Experimental and Computational Modeling of the Anticancer Effects of Cnidocyte Venoms of Jellyfish Cassiopea andromeda and Catostylus mosaicus on Human Adenocarcinoma A549 Cells
by Afshin Zare, Alireza Afshar, Arezoo Khoradmehr, Neda Baghban, Gholamhossein Mohebbi, Alireza Barmak, Adel Daneshi, Afshar Bargahi, Iraj Nabipour, Sahar Almasi-Turk, Alireza Arandian, Mohammad Ismail Zibaii, Hamid Latifi and Amin Tamadon
Mar. Drugs 2023, 21(3), 168; https://doi.org/10.3390/md21030168 - 07 Mar 2023
Cited by 4 | Viewed by 2296
Abstract
Nowadays, major attention is being paid to curing different types of cancers and is focused on natural resources, including oceans and marine environments. Jellyfish are marine animals with the ability to utilize their venom in order to both feed and defend. Prior studies [...] Read more.
Nowadays, major attention is being paid to curing different types of cancers and is focused on natural resources, including oceans and marine environments. Jellyfish are marine animals with the ability to utilize their venom in order to both feed and defend. Prior studies have displayed the anticancer capabilities of various jellyfish. Hence, we examined the anticancer features of the venom of Cassiopea andromeda and Catostylus mosaicus in an in vitro situation against the human pulmonary adenocarcinoma (A549) cancer cell line. The MTT assay demonstrated that both mentioned venoms have anti-tumoral ability in a dose-dependent manner. Western blot analysis proved that both venoms can increase some pro-apoptotic factors and reduce some anti-apoptotic molecules that lead to the inducing of apoptosis in A549 cells. GC/MS analysis demonstrated some compounds with biological effects, including anti-inflammatory, antioxidant and anti-cancer activities. Molecular docking and molecular dynamic showed the best position of each biologically active component on the different death receptors, which are involved in the process of apoptosis in A549 cells. Ultimately, this study has proven that both venoms of C. andromeda and C. mosaicus have the capability to suppress A549 cells in an in vitro condition and they might be utilized in order to design and develop brand new anticancer agents in the near future. Full article
(This article belongs to the Special Issue Marine Compounds and Research of the Middle East)
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