Marine Drugs

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Open AccessArticle

Peptides, Peptidomimetics, and Polypeptides from Marine Sources: A Wealth of Natural Sources for Pharmaceutical Applications

by Rushikesh Sable, Pravin Parajuli and Seetharama Jois

Mar. Drugs 2017, 15(4), 124; https://doi.org/10.3390/md15040124 - 22 Apr 2017

Cited by 103 | Viewed by 13774

Abstract

Nature provides a variety of peptides that are expressed in most living species. Evolutionary pressure and natural selection have created and optimized these peptides to bind to receptors with high affinity. Hence, natural resources provide an abundant chemical space to be explored in [...] Read more.

Nature provides a variety of peptides that are expressed in most living species. Evolutionary pressure and natural selection have created and optimized these peptides to bind to receptors with high affinity. Hence, natural resources provide an abundant chemical space to be explored in peptide-based drug discovery. Marine peptides can be extracted by simple solvent extraction techniques. The advancement of analytical techniques has made it possible to obtain pure peptides from natural resources. Extracted peptides have been evaluated as possible therapeutic agents for a wide range of diseases, including antibacterial, antifungal, antidiabetic and anticancer activity as well as cardiovascular and neurotoxin activity. Although marine resources provide thousands of possible peptides, only a few peptides derived from marine sources have reached the pharmaceutical market. This review focuses on some of the peptides derived from marine sources in the past ten years and gives a brief review of those that are currently in clinical trials or on the market. Full article

(This article belongs to the Special Issue Drug Design Based on Marine Natural Product Scaffolds)

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Open AccessArticle

Identification of Tight-Binding Plasmepsin II and Falcipain 2 Inhibitors in Aqueous Extracts of Marine Invertebrates by the Combination of Enzymatic and Interaction-Based Assays

by Emir Salas-Sarduy, Yasel Guerra, Giovanni Covaleda Cortés, Francesc Xavier Avilés and María A. Chávez Planes

Mar. Drugs 2017, 15(4), 123; https://doi.org/10.3390/md15040123 - 21 Apr 2017

Cited by 7 | Viewed by 4937

Abstract

Natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. However, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous [...] Read more.

Natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. However, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous and interfering context. In the present study, we describe a general strategy for the confident identification of tight-binding protease inhibitors in the aqueous extracts of 62 Cuban marine invertebrates, using Plasmodium falciparum hemoglobinases Plasmepsin II and Falcipain 2 as model enzymes. To this end, we first developed a screening strategy that combined enzymatic with interaction-based assays and then validated screening conditions using five reference extracts. Interferences were evaluated and minimized. The results from the massive screening of such extracts, the validation of several hits by a variety of interaction-based assays and the purification and functional characterization of PhPI, a multifunctional and reversible tight-binding inhibitor for Plasmepsin II and Falcipain 2 from the gorgonian Plexaura homomalla, are presented. Full article

(This article belongs to the Special Issue Enzyme Inhibitors of Marine Origin)

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Open AccessArticle

Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial

by Hsiang-Lin Tsai, Chi-Jung Tai, Ching-Wen Huang, Fang-Rong Chang and Jaw-Yuan Wang

Mar. Drugs 2017, 15(4), 122; https://doi.org/10.3390/md15040122 - 21 Apr 2017

Cited by 101 | Viewed by 10908

Abstract

Background: Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical evidence for LMF use is relatively weak. This study aimed to evaluate the [...] Read more.

Background: Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical evidence for LMF use is relatively weak. This study aimed to evaluate the efficacy of LMF as a supplemental therapy to chemo-target agents in metastatic colorectal cancer (mCRC) patients. Methods: We conducted a prospective, randomized, double-blind, controlled trial to evaluate the efficacy of LMF as a supplemental therapy to chemotarget agents in patients with metastatic colorectal cancer (mCRC). Sixty eligible patients with mCRC were included. Finally, 54 patients were enrolled, of whom 28 were included in the study group and 26 in the control group. The primary endpoint was the disease control rate (DCR), and secondary endpoints included the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and quality of life (QOL). Results: The DCRs were 92.8% and 69.2% in the study and control groups, respectively (p = 0.026), in a median follow-up period of 11.5 months. The OS, PFS, ORR, AEs, and QOL did not significantly differ between the two groups. Conclusion: This is the first clinical trial evaluating the efficacy of LMF as a supplemental therapy in the management of patients with mCRC. The results indicate that LMF combined with chemotarget agents significantly improved the DCR. Full article

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Open AccessFeature PaperArticle

Laucysteinamide A, a Hybrid PKS/NRPS Metabolite from a Saipan Cyanobacterium, cf. Caldora penicillata

by Chen Zhang, C. Benjamin Naman, Niclas Engene and William H. Gerwick

Mar. Drugs 2017, 15(4), 121; https://doi.org/10.3390/md15040121 - 14 Apr 2017

Cited by 18 | Viewed by 5991

Abstract

A bioactivity guided study of a cf. Caldora penicillata species, collected during a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a commonwealth of the USA), led to the isolation of a new thiazoline-containing alkaloid, laucysteinamide A (1). [...] Read more.

A bioactivity guided study of a cf. Caldora penicillata species, collected during a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a commonwealth of the USA), led to the isolation of a new thiazoline-containing alkaloid, laucysteinamide A (1). Laucysteinamide A is a new monomeric analogue of the marine cyanobacterial metabolite, somocystinamide A (2), a disulfide-bonded dimeric compound that was isolated previously from a Fijian marine cyanobacterium. The structure and absolute configuration of laucysteinamide A (1) was determined by a detailed analysis of its NMR, MS, and CD spectra. In addition, the highly bioactive lipid, curacin D (3), was also found to be present in this cyanobacterial extract. The latter compound was responsible for the potent cytotoxicity of this extract to H-460 human non-small cell lung cancer cells in vitro. Full article

(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)

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Open AccessArticle

New Cytotoxic Secondary Metabolites from Marine Bryozoan Cryptosula pallasiana

by Xiang-Rong Tian, Yan-Qing Gao, Xiao-Lin Tian, Jiao Li, Hai-Feng Tang, Yu-Shan Li, Hou-Wen Lin and Zhi-Qing Ma

Mar. Drugs 2017, 15(4), 120; https://doi.org/10.3390/md15040120 - 13 Apr 2017

Cited by 8 | Viewed by 4412

Abstract

A new sterol, (23R)-methoxycholest-5,24-dien-3β-ol (1), two new ceramides, (2S,3R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3-diol (6) and (2S,3R,2′R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3,2′-triol (7), together with three known [...] Read more.

A new sterol, (23R)-methoxycholest-5,24-dien-3β-ol (1), two new ceramides, (2S,3R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3-diol (6) and (2S,3R,2′R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3,2′-triol (7), together with three known sterols (2–4), a lactone (5) and two ceramides (8,9), were isolated from the marine bryozoan Cryptosula pallasiana, collected at Huang Island of China. The structures of the new compounds were elucidated by extensive spectroscopic analyses, chemical methods and quantum electronic circular dichroism (ECD) calculations. Among the isolated compounds, sterol 1 possessed a rare side chain with a methoxy group at C-23, and a double bond between C-24 and C-25. Ceramides 6 and 7 possessed 14 carbons in their long-chain fatty acid base (FAB), which were different from the normal ceramides with 16 carbons in the FAB. Moreover, compounds 5 and 8 were isolated for the first time from marine bryozoans. Compounds 1–9 were evaluated for their cytotoxicity against human tumor cell lines HL-60, Hep-G2 and SGC-7901. The results showed that lactone 5 appears to have strong cytotoxicity against the test tumor cell lines, with IC₅₀ values from 4.12 μM to 7.32 μM, and sterol 1 displayed moderate cytotoxicity with IC₅₀ values between 12.34 μM and 18.37 μM, while ceramides 6–9 showed weak cytotoxicity with IC₅₀ ranging from 21.13 μM to 58.15 μM. Full article

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Open AccessArticle

Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit Adipogenesis through AMPK Activation in 3T3-L1 Preadipocytes

by Min-Cheol Kang, Yuling Ding, Eun-A Kim, Youn Kyung Choi, Thiago De Araujo, Soo-Jin Heo and Seung-Hong Lee

Mar. Drugs 2017, 15(4), 119; https://doi.org/10.3390/md15040119 - 12 Apr 2017

Cited by 49 | Viewed by 6688

Abstract

Seaweed, a popular and abundant food ingredient mainly consumed in Asian countries, is a good source of bioactive compounds with anti-obesity effects. However, the anti-obesity effects of Sargassum thunbergii have not yet been established. In this study, we isolated six indole derivatives (STCs)—indole-2-carboxaldehyde [...] Read more.

Seaweed, a popular and abundant food ingredient mainly consumed in Asian countries, is a good source of bioactive compounds with anti-obesity effects. However, the anti-obesity effects of Sargassum thunbergii have not yet been established. In this study, we isolated six indole derivatives (STCs)—indole-2-carboxaldehyde (STC-1), indole-3-carboxaldehyde (STC-2), indole-4-carboxaldehyde (STC-3), indole-5-carboxaldehyde (STC-4), indole-6-carboxaldehyde (STC-5), and indole-7-carboxaldehyde (STC-6)—from S. thunbergii and evaluated their inhibitory effects on adipocyte differentiation in 3T3-L1 cells. We found that STC-1 and STC-5 resulted in non-toxic inhibition of the differentiation of 3T3-L1 adipocytes and thus selected these compounds for further study. STC-1 and STC-5 significantly inhibited lipid accumulation and downregulated the expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1c (SREBP-1c) in a dose-dependent manner. The specific mechanism mediating the effects of STC-1 and STC-5 was shown to be AMP-activated protein kinase (AMPK) activation. Our results demonstrated the inhibitory effect of STC-1 and STC-5 on adipogenesis through the activation of the AMPK signal pathway. Together, these findings suggested that STC-1 and STC-5 may be effective candidates for the prevention of obesity or obesity-related diseases. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)

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Open AccessReview

Marine Microbial-Derived Molecules and Their Potential Use in Cosmeceutical and Cosmetic Products

by Cinzia Corinaldesi, Giulio Barone, Francesca Marcellini, Antonio Dell’Anno and Roberto Danovaro

Mar. Drugs 2017, 15(4), 118; https://doi.org/10.3390/md15040118 - 12 Apr 2017

Cited by 130 | Viewed by 14618

Abstract

The oceans encompass a wide range of habitats and environmental conditions, which host a huge microbial biodiversity. The unique characteristics of several marine systems have driven a variety of biological adaptations, leading to the production of a large spectrum of bioactive molecules. Fungi, [...] Read more.

The oceans encompass a wide range of habitats and environmental conditions, which host a huge microbial biodiversity. The unique characteristics of several marine systems have driven a variety of biological adaptations, leading to the production of a large spectrum of bioactive molecules. Fungi, fungi-like protists (such as thraustochytrids) and bacteria are among the marine organisms with the highest potential of producing bioactive compounds, which can be exploited for several commercial purposes, including cosmetic and cosmeceutical ones. Mycosporines and mycosporine-like amino acids, carotenoids, exopolysaccharides, fatty acids, chitosan and other compounds from these microorganisms might represent a sustainable, low-cost and fast-production alternative to other natural molecules used in photo-protective, anti-aging and skin-whitening products for face, body and hair care. Here, we review the existing knowledge of these compounds produced by marine microorganisms, highlighting the marine habitats where such compounds are preferentially produced and their potential application in cosmetic and cosmeceutical fields. Full article

(This article belongs to the Special Issue Biotransformations Utilizing Marine/Marine-Derived Bacteria and Fungi)

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Open AccessArticle

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles

by Zongrui Tong, Yu Chen, Yang Liu, Li Tong, Jiamian Chu, Kecen Xiao, Zhiyu Zhou, Wenbo Dong and Xingwu Chu

Mar. Drugs 2017, 15(4), 91; https://doi.org/10.3390/md15040091 - 11 Apr 2017

Cited by 72 | Viewed by 6719

Abstract

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) [...] Read more.

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca²⁺ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates. Full article

(This article belongs to the Collection Marine Polysaccharides)

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Open AccessFeature PaperArticle

Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia

by Idam Hermawan, Atsushi Furuta, Masahiro Higashi, Yoshihisa Fujita, Nobuyoshi Akimitsu, Atsuya Yamashita, Kohji Moriishi, Satoshi Tsuneda, Hidenori Tani, Masamichi Nakakoshi, Masayoshi Tsubuki, Yuji Sekiguchi, Naohiro Noda and Junichi Tanaka

Mar. Drugs 2017, 15(4), 117; https://doi.org/10.3390/md15040117 - 11 Apr 2017

Cited by 10 | Viewed by 5439

Abstract

Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia, inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 1–4. The structures of the aromatics were elucidated by [...] Read more.

Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia, inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 1–4. The structures of the aromatics were elucidated by spectroscopic analysis in addition to theoretical studies. The aromatic sulfates 1–4 showed moderate inhibition against NS3 helicase with IC₅₀ values of 71, 95, 7, and 5 μM, respectively. Full article

(This article belongs to the Special Issue Bioactive Marine Natural Compounds with Heterocyclic Motifs in their Structure)

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Open AccessCommunication

Cloning and Functional Characterization of a Lycopene β-Cyclase from Macrophytic Red Alga Bangia fuscopurpurea

by Tian-Jun Cao, Xing-Qi Huang, Yuan-Yuan Qu, Zhong Zhuang, Yin-Yin Deng and Shan Lu

Mar. Drugs 2017, 15(4), 116; https://doi.org/10.3390/md15040116 - 11 Apr 2017

Cited by 12 | Viewed by 6393

Abstract

Lycopene cyclases cyclize the open ends of acyclic lycopene (ψ,ψ-carotene) into β- or ε-ionone rings in the crucial bifurcation step of carotenoid biosynthesis. Among all carotenoid constituents, β-carotene (β,β-carotene) is found in all photosynthetic organisms, except for purple bacteria and heliobacteria, suggesting a [...] Read more.

Lycopene cyclases cyclize the open ends of acyclic lycopene (ψ,ψ-carotene) into β- or ε-ionone rings in the crucial bifurcation step of carotenoid biosynthesis. Among all carotenoid constituents, β-carotene (β,β-carotene) is found in all photosynthetic organisms, except for purple bacteria and heliobacteria, suggesting a ubiquitous distribution of lycopene β-cyclase activity in these organisms. In this work, we isolated a gene (BfLCYB) encoding a lycopene β-cyclase from Bangia fuscopurpurea, a red alga that is considered to be one of the primitive multicellular eukaryotic photosynthetic organisms and accumulates carotenoid constituents with both β- and ε-rings, including β-carotene, zeaxanthin, α-carotene (β,ε-carotene) and lutein. Functional complementation in Escherichia coli demonstrated that BfLCYB is able to catalyze cyclization of lycopene into monocyclic γ-carotene (β,ψ-carotene) and bicyclic β-carotene, and cyclization of the open end of monocyclic δ-carotene (ε,ψ-carotene) to produce α-carotene. No ε-cyclization activity was identified for BfLCYB. Sequence comparison showed that BfLCYB shares conserved domains with other functionally characterized lycopene cyclases from different organisms and belongs to a group of ancient lycopene cyclases. Although B. fuscopurpurea also synthesizes α-carotene and lutein, its enzyme-catalyzing ε-cyclization is still unknown. Full article

(This article belongs to the Special Issue Marine Carotenoids)

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Open AccessArticle

In Vitro Antioxidant Activities of Enzymatic Hydrolysate from Schizochytrium sp. and Its Hepatoprotective Effects on Acute Alcohol-Induced Liver Injury In Vivo

by Xixi Cai, Ana Yan, Nanyan Fu and Shaoyun Wang

Mar. Drugs 2017, 15(4), 115; https://doi.org/10.3390/md15040115 - 10 Apr 2017

Cited by 37 | Viewed by 5336

Abstract

Schizochytrium protein hydrolysate (SPH) was prepared through stepwise enzymatic hydrolysis by alcalase and flavourzyme sequentially. The proportion of hydrophobic amino acids of SPH was 34.71%. The molecular weight (MW) of SPH was principally concentrated at 180–3000 Da (52.29%). SPH was divided into two [...] Read more.

Schizochytrium protein hydrolysate (SPH) was prepared through stepwise enzymatic hydrolysis by alcalase and flavourzyme sequentially. The proportion of hydrophobic amino acids of SPH was 34.71%. The molecular weight (MW) of SPH was principally concentrated at 180–3000 Da (52.29%). SPH was divided into two fractions by ultrafiltration: SPH-I (MW < 3 kDa) and SPH-II (MW > 3 kDa). Besides showing lipid peroxidation inhibitory activity in vitro, SPH-I exhibited high DPPH and ABTS radicals scavenging activities with IC₅₀ of 350 μg/mL and 17.5 μg/mL, respectively. In addition, the antioxidant activity of SPH-I was estimated in vivo using the model of acute alcohol-induced liver injury in mice. For the hepatoprotective effects, oral administration of SPH-I at different concentrations (100, 300 mg/kg BW) to the mice subjected to alcohol significantly decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA) level compared to the untreated mice. Besides, SPH-I could effectively restore the hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and glutathione (GSH) level. Results suggested that SPH was rich in biopeptides that could be exploited as antioxidant molecules against oxidative stress in human body. Full article

(This article belongs to the Special Issue Marine Proteins and Peptides)

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Open AccessArticle

Prospecting Biotechnologically-Relevant Monooxygenases from Cold Sediment Metagenomes: An In Silico Approach

by Matías A. Musumeci, Mariana Lozada, Daniela V. Rial, Walter P. Mac Cormack, Janet K. Jansson, Sara Sjöling, JoLynn Carroll and Hebe M. Dionisi

Mar. Drugs 2017, 15(4), 114; https://doi.org/10.3390/md15040114 - 9 Apr 2017

Cited by 14 | Viewed by 6345

Abstract

The goal of this work was to identify sequences encoding monooxygenase biocatalysts with novel features by in silico mining an assembled metagenomic dataset of polar and subpolar marine sediments. The targeted enzyme sequences were Baeyer–Villiger and bacterial cytochrome P450 monooxygenases (CYP153). These enzymes [...] Read more.

The goal of this work was to identify sequences encoding monooxygenase biocatalysts with novel features by in silico mining an assembled metagenomic dataset of polar and subpolar marine sediments. The targeted enzyme sequences were Baeyer–Villiger and bacterial cytochrome P450 monooxygenases (CYP153). These enzymes have wide-ranging applications, from the synthesis of steroids, antibiotics, mycotoxins and pheromones to the synthesis of monomers for polymerization and anticancer precursors, due to their extraordinary enantio-, regio-, and chemo- selectivity that are valuable features for organic synthesis. Phylogenetic analyses were used to select the most divergent sequences affiliated to these enzyme families among the 264 putative monooxygenases recovered from the ~14 million protein-coding sequences in the assembled metagenome dataset. Three-dimensional structure modeling and docking analysis suggested features useful in biotechnological applications in five metagenomic sequences, such as wide substrate range, novel substrate specificity or regioselectivity. Further analysis revealed structural features associated with psychrophilic enzymes, such as broader substrate accessibility, larger catalytic pockets or low domain interactions, suggesting that they could be applied in biooxidations at room or low temperatures, saving costs inherent to energy consumption. This work allowed the identification of putative enzyme candidates with promising features from metagenomes, providing a suitable starting point for further developments. Full article

(This article belongs to the Special Issue Biotransformations Utilizing Marine/Marine-Derived Bacteria and Fungi)

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Open AccessArticle

Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes

by Hong-Ting Victor Lin, Yu-Chi Tsou, Yu-Ting Chen, Wen-Jung Lu and Pai-An Hwang

Mar. Drugs 2017, 15(4), 113; https://doi.org/10.3390/md15040113 - 7 Apr 2017

Cited by 91 | Viewed by 8096

Abstract

The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting [...] Read more.

The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS)-1, glucose transporter (GLUT), peroxisome proliferator-activated receptor gamma (PPARγ), and uncoupling protein (UCP)-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx. Full article

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Open AccessArticle

Promoting Wound Healing Using Low Molecular Weight Fucoidan in a Full-Thickness Dermal Excision Rat Model

by Jun-Hyeong Park, Seong-Hun Choi, Soo-Jin Park, Young Joon Lee, Jong Hyun Park, Phil Hyun Song, Chang-Mo Cho, Sae-Kwang Ku and Chang-Hyun Song

Mar. Drugs 2017, 15(4), 112; https://doi.org/10.3390/md15040112 - 7 Apr 2017

Cited by 81 | Viewed by 8299

Abstract

Low molecular weight fucoidan (LMF) has been reported to possess anti-inflammatory and antioxidant activities. Thus, we examined the effects of LMF extracted from Undaria pinnatifida on dermal wounds. Five round dermal wounds were created on the dorsal back of rats, and they were [...] Read more.

Low molecular weight fucoidan (LMF) has been reported to possess anti-inflammatory and antioxidant activities. Thus, we examined the effects of LMF extracted from Undaria pinnatifida on dermal wounds. Five round dermal wounds were created on the dorsal back of rats, and they were then treated topically with distilled water (DW), Madecasol Care™ (MC) or LMF at 200, 100 and 50 mg/mL, twice a day for a week. There were dose-dependent increases in wound contraction in the groups receiving LMF but not in the MC group, compared with the DW. Histopathological examination revealed that LMF treatment accelerated wound healing, which was supported by increases in granular tissue formation on day four post-treatment but a decrease on day seven, accompanied by an evident reduction in inflammatory cells. In the LMF-treated wounds, collagen distribution and angiogenesis were increased in the granular tissue on days four and seven post-treatment. Immunoreactive cells for transforming growth factor-β1, vascular endothelial growth factor receptor-2 or matrix metalloproteinases 9 were also increased, probably due to tissue remodeling. Furthermore, LMF treatment reduced lipid peroxidation and increased antioxidant activities. These suggested that LMF promotes dermal wound healing via complex and coordinated antioxidant, anti-inflammatory and growth factor-dependent activities. Full article

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Open AccessArticle

Bioactive Metabolites from the Deep Subseafloor Fungus Oidiodendron griseum UBOCC-A-114129

by Marion Navarri, Camille Jégou, Arnaud Bondon, Sandrine Pottier, Stéphane Bach, Blandine Baratte, Sandrine Ruchaud, Georges Barbier, Gaëtan Burgaud and Yannick Fleury

Mar. Drugs 2017, 15(4), 111; https://doi.org/10.3390/md15040111 - 7 Apr 2017

Cited by 15 | Viewed by 4612

Abstract

Four bioactive compounds have been isolated from the fungus Oidiodendron griseum UBOCC-A-114129 cultivated from deep subsurface sediment. They were structurally characterized using a combination of LC–MS/MS and NMR analyses as fuscin and its derivatives (dihydrofuscin, dihydrosecofuscin, and secofuscin) and identified as polyketides. Albeit [...] Read more.

Four bioactive compounds have been isolated from the fungus Oidiodendron griseum UBOCC-A-114129 cultivated from deep subsurface sediment. They were structurally characterized using a combination of LC–MS/MS and NMR analyses as fuscin and its derivatives (dihydrofuscin, dihydrosecofuscin, and secofuscin) and identified as polyketides. Albeit those compounds were already obtained from terrestrial fungi, this is the first report of their production by an Oidiodendron species and by the deepest subseafloor isolate ever studied for biological activities. We report a weak antibacterial activity of dihydrosecofuscin and secofuscin mainly directed against Gram-positive bacteria (Minimum Inhibitory Concentration (MIC) equal to Minimum Bactericidal Concentration (MBC), in the range of 100 μg/mL). The activity on various protein kinases was also analyzed and revealed a significant inhibition of CDC2-like kinase-1 (CLK1) by dihysecofuscin. Full article

(This article belongs to the Special Issue Marine Fungal Natural Products)

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Open AccessArticle

Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H₂O₂-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway

by Jing Wang, Huaide Liu, Xuan Zhang, Xinpeng Li, Lihua Geng, Hong Zhang and Quanbin Zhang

Mar. Drugs 2017, 15(4), 110; https://doi.org/10.3390/md15040110 - 6 Apr 2017

Cited by 31 | Viewed by 5760

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of [...] Read more.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H₂O₂-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3β, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD. Full article

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Open AccessArticle

An Unusual Diterpene—Enhygromic Acid and Deoxyenhygrolides from a Marine Myxobacterium, Enhygromyxa sp.

by Tomohiko Tomura, Shiori Nagashima, Satoshi Yamazaki, Takashi Iizuka, Ryosuke Fudou and Makoto Ojika

Mar. Drugs 2017, 15(4), 109; https://doi.org/10.3390/md15040109 - 6 Apr 2017

Cited by 18 | Viewed by 5107

Abstract

Three new compounds, enhygromic acid (1) and deoxyenhygrolides A (2) and B (3), were isolated from a marine myxobacterium, Enhygromyxa sp. Compound 1 was found to be an acrylic acid derivative with a rare polycyclic carbon skeleton, [...] Read more.

Three new compounds, enhygromic acid (1) and deoxyenhygrolides A (2) and B (3), were isolated from a marine myxobacterium, Enhygromyxa sp. Compound 1 was found to be an acrylic acid derivative with a rare polycyclic carbon skeleton, decahydroacenaphthylene, by spectroscopic analyses. Compounds 2 and 3 were deoxy analogs of the known γ-alkylidenebutenolides, enhygrolides. Compound 1 exhibited cytotoxicity against B16 melanoma cells and anti-bacterial activity against Bacillus subtilis, and enhanced the NGF-induced neurite outgrowth of PC12 cells. Full article

(This article belongs to the Special Issue Marine Bioactive Natural Product Studies in Asia)

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Open AccessArticle

Lindane Bioremediation Capability of Bacteria Associated with the Demosponge Hymeniacidon perlevis

by Stabili Loredana, Pizzolante Graziano, Morgante Antonio, Nonnis Marzano Carlotta, Longo Caterina, Aresta Antonella Maria, Zambonin Carlo, Corriero Giuseppe and Alifano Pietro

Mar. Drugs 2017, 15(4), 108; https://doi.org/10.3390/md15040108 - 6 Apr 2017

Cited by 19 | Viewed by 6203

Abstract

Lindane is an organochlorine pesticide belonging to persistent organic pollutants (POPs) that has been widely used to treat agricultural pests. It is of particular concern because of its toxicity, persistence and tendency to bioaccumulate in terrestrial and aquatic ecosystems. In this context, we [...] Read more.

Lindane is an organochlorine pesticide belonging to persistent organic pollutants (POPs) that has been widely used to treat agricultural pests. It is of particular concern because of its toxicity, persistence and tendency to bioaccumulate in terrestrial and aquatic ecosystems. In this context, we assessed the role of bacteria associated with the sponge Hymeniacidon perlevis in lindane degradation. Seven bacteria isolates were characterized and identified. These isolates showed a remarkable capacity to utilize lindane as a sole carbon source leading to a percentage of residual lindane ranging from 3% to 13% after 12 days of incubation with the pesticide. The lindane metabolite, 1,3–6-pentachloro-cyclohexene, was identified as result of lindane degradation and determined by gas chromatography–mass spectrometry (GC–MS). The bacteria capable of lindane degradation were identified on the basis of the phenotypic characterization by morphological, biochemical and cultural tests, completed with 16S rDNA sequence analysis, and assigned to Mameliella phaeodactyli, Pseudovibrio ascidiaceicola, Oceanicaulis stylophorae, Ruegeria atlantica and to three new uncharacterized species. The results obtained are a prelude to the development of future strategies for the in situ bioremediation of lindane. Full article

(This article belongs to the Special Issue Biotransformations Utilizing Marine/Marine-Derived Bacteria and Fungi)

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Open AccessArticle

Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum

by Yongze Yuan, Rui Han, Qianwen Cao, Jinhui Yu, Jiali Mao, Tingfu Zhang, Shengqiang Wang, Yuhui Niu and Deli Liu

Mar. Drugs 2017, 15(4), 107; https://doi.org/10.3390/md15040107 - 5 Apr 2017

Cited by 10 | Viewed by 5591

Abstract

Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from Penicillium italicum (PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A [...] Read more.

Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from Penicillium italicum (PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A (PDB: 3LD6). Molecular dynamics (MD) simulation was operated to relax the initial model and followed by quality assessment using PROCHECK program. On the basis of the docking information on the currently available CYP51s with the patent demethylase inhibitors (DMIs), pharmacophore-based virtual screening combined with docking analysis was performed to pick out twelve new compounds from ZINC database. Six hits revealed in the ligand database suggested potential ability to inhibit PiCYP51A. Compared to patent fungicide triazolone, the top three lead compounds had similar or higher affinity with the target enzyme, and accordingly, exhibited comparable or lower EC₅₀ values to P. italicum isolates. The results could provide references for de novo antifungal drug design. Full article

(This article belongs to the Special Issue Selected Papers from the International Conference on Coastal Ecology and Marine Biotechnology Dec. 8-10, 2016 Bangkok, Thailand)

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Open AccessArticle

The Effect of Phloroglucinol, A Component of Ecklonia cava Extract, on Hepatic Glucose Production

by Ji-Young Yoon, Hojung Choi and Hee-Sook Jun

Mar. Drugs 2017, 15(4), 106; https://doi.org/10.3390/md15040106 - 5 Apr 2017

Cited by 39 | Viewed by 6308

Abstract

Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control [...] Read more.

Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control of blood glucose levels and the regulation of hepatic glucose production. Phloroglucinol significantly improved glucose tolerance in male C57BL/6J mice fed a high fat diet (HFD) and inhibited glucose production in mouse primary hepatocytes. The expression of phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase mRNA and protein (G6Pase), enzymes involved in gluconeogenesis, were inhibited in liver tissue from phloroglucinol-treated mice and in phloroglucinol-treated HepG2 cells. In addition, phloroglucinol treatment increased phosphorylated AMP-activated protein kinase (AMPK)α in HepG2 cells. Treatment with compound C, an AMPKα inhibitor, inhibited the increase of phosphorylated AMPKα and the decrease of PEPCK and G6Pase expression caused by phloroglucinol treatment. We conclude that phloroglucinol may inhibit hepatic gluconeogenesis via modulating the AMPKα signaling pathway, and thus lower blood glucose levels. Full article

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Open AccessArticle

Fluorescent Property of Chitosan Oligomer and Its Application as a Metal Ion Sensor

by Hun Min Lee, Min Hee Kim, Young Il Yoon and Won Ho Park

Mar. Drugs 2017, 15(4), 105; https://doi.org/10.3390/md15040105 - 4 Apr 2017

Cited by 40 | Viewed by 7464

Abstract

An aqueous solution was successfully prepared using a low-molecular-weight chitosan oligomer and FITC, and its structural and fluorescent properties were observed by using ¹H NMR, ¹³C NMR, FT-IR, XRD, UV-Vis, and PL spectrometry. Its application as a metal ion sensor was [...] Read more.

An aqueous solution was successfully prepared using a low-molecular-weight chitosan oligomer and FITC, and its structural and fluorescent properties were observed by using ¹H NMR, ¹³C NMR, FT-IR, XRD, UV-Vis, and PL spectrometry. Its application as a metal ion sensor was also evaluated. The fluorescence in the water-soluble chitosan oligomer was a result of the carbamato anion (NHCOO-), and a synthesized FITC-labeled chitosan oligomer exhibited an effective detection effect for copper ion as well as energy transfer by the ion near FITC that caused a fluorescence decrease (quenching). The chitosan oligomer was confirmed to be applicable as a selective and sensitive colorimetric sensor to detect Cu²⁺. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

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Open AccessArticle

Optimization of Bromelain-Aided Production of Angiotensin I-Converting Enzyme Inhibitory Hydrolysates from Stone Fish Using Response Surface Methodology

by Shehu Muhammad Auwal, Mohammad Zarei, Azizah Abdul-Hamid and Nazamid Saari

Mar. Drugs 2017, 15(4), 104; https://doi.org/10.3390/md15040104 - 31 Mar 2017

Cited by 41 | Viewed by 6306

Abstract

The stone fish is an under-utilized sea cucumber with many nutritional and ethno-medicinal values. This study aimed to establish the conditions for its optimum hydrolysis with bromelain to generate angiotensin I-converting enzyme (ACE)-inhibitory hydrolysates. Response surface methodology (RSM) based on a central composite [...] Read more.

The stone fish is an under-utilized sea cucumber with many nutritional and ethno-medicinal values. This study aimed to establish the conditions for its optimum hydrolysis with bromelain to generate angiotensin I-converting enzyme (ACE)-inhibitory hydrolysates. Response surface methodology (RSM) based on a central composite design was used to model and optimize the degree of hydrolysis (DH) and ACE-inhibitory activity. Process conditions including pH (4–7), temperature (40–70 °C), enzyme/substrate (E/S) ratio (0.5%–2%) and time (30–360 min) were used. A pH of 7.0, temperature of 40 °C, E/S ratio of 2% and time of 240 min were determined using a response surface model as the optimum levels to obtain the maximum ACE-inhibitory activity of 84.26% at 44.59% degree of hydrolysis. Hence, RSM can serve as an effective approach in the design of experiments to improve the antihypertensive effect of stone fish hydrolysates, which can thus be used as a value-added ingredient for various applications in the functional foods industries. Full article

(This article belongs to the Special Issue Enzyme Inhibitors of Marine Origin)

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Open AccessReview

From Marine Venoms to Drugs: Efficiently Supported by a Combination of Transcriptomics and Proteomics

by Bing Xie, Yu Huang, Kate Baumann, Bryan Grieg Fry and Qiong Shi

Mar. Drugs 2017, 15(4), 103; https://doi.org/10.3390/md15040103 - 30 Mar 2017

Cited by 27 | Viewed by 6428

Abstract

The potential of marine natural products to become new drugs is vast; however, research is still in its infancy. The chemical and biological diversity of marine toxins is immeasurable and as such an extraordinary resource for the discovery of new drugs. With the [...] Read more.

The potential of marine natural products to become new drugs is vast; however, research is still in its infancy. The chemical and biological diversity of marine toxins is immeasurable and as such an extraordinary resource for the discovery of new drugs. With the rapid development of next-generation sequencing (NGS) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), it has been much easier and faster to identify more toxins and predict their functions with bioinformatics pipelines, which pave the way for novel drug developments. Here we provide an overview of related bioinformatics pipelines that have been supported by a combination of transcriptomics and proteomics for identification and function prediction of novel marine toxins. Full article

(This article belongs to the Special Issue Marine Natural Product Discovery: Innovative Strategies and Future Trends)

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Open AccessArticle

Marine Collagen Peptides from the Skin of Nile Tilapia (Oreochromis niloticus): Characterization and Wound Healing Evaluation

by Zhang Hu, Ping Yang, Chunxia Zhou, Sidong Li and Pengzhi Hong

Mar. Drugs 2017, 15(4), 102; https://doi.org/10.3390/md15040102 - 30 Mar 2017

Cited by 177 | Viewed by 18047

Abstract

Burns can cause tremendous economic problems associated with irreparable harm to patients and their families. To characterize marine collagen peptides (MCPs) from the skin of Nile tilapia (Oreochromis niloticus), molecular weight distribution and amino acid composition of MCPs were determined, and [...] Read more.

Burns can cause tremendous economic problems associated with irreparable harm to patients and their families. To characterize marine collagen peptides (MCPs) from the skin of Nile tilapia (Oreochromis niloticus), molecular weight distribution and amino acid composition of MCPs were determined, and Fourier transform infrared spectroscopy (FTIR) was used to analyze the chemical structure. Meanwhile, to evaluate the wound healing activity, in vitro and in vivo experiments were carried out. The results showed that MCPs prepared from the skin of Nile tilapia by composite enzymatic hydrolysis were composed of polypeptides with different molecular weights and the contents of polypeptides with molecular weights of less than 5 kDa accounted for 99.14%. From the amino acid composition, the majority of residues, accounting for over 58% of the total residues in MCPs, were hydrophilic. FTIR indicated that the main molecular conformations inside MCPs were random coil. In vitro scratch assay showed that there were significant effects on the scratch closure by the treatment of MCPs with the concentration of 50.0 μg/mL. In the experiments of deep partial-thickness scald wound in rabbits, MCPs could enhance the process of wound healing. Therefore, MCPs from the skin of Nile tilapia (O. niloticus) have promising applications in wound care. Full article

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Open AccessArticle

The Influence of Tetrodotoxin (TTX) on the Distribution and Chemical Coding of Caudal Mesenteric Ganglion (CaMG) Neurons Supplying the Porcine Urinary Bladder

by Ewa Lepiarczyk, Agnieszka Bossowska, Jerzy Kaleczyc, Marta Majewska, Sławomir Gonkowski and Mariusz Majewski

Mar. Drugs 2017, 15(4), 101; https://doi.org/10.3390/md15040101 - 30 Mar 2017

Cited by 4 | Viewed by 4073

Abstract

The treatment of micturition disorders creates a serious problem for urologists. Recently, new therapeutic agents, such as neurotoxins, are being considered for the therapy of urological patients. The present study investigated the chemical coding of caudal mesenteric ganglion (CaMG) neurons supplying the porcine [...] Read more.

The treatment of micturition disorders creates a serious problem for urologists. Recently, new therapeutic agents, such as neurotoxins, are being considered for the therapy of urological patients. The present study investigated the chemical coding of caudal mesenteric ganglion (CaMG) neurons supplying the porcine urinary bladder after intravesical instillation of tetrodotoxin (TTX). The CaMG neurons were visualized with retrograde tracer Fast blue (FB) and their chemical profile was disclosed with double-labeling immunohistochemistry using antibodies against tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), calbindin (CB), galanin (GAL) and neuronal nitric oxide synthase (nNOS). It was found that in both the control (n = 6) and TTX-treated pigs (n = 6), the vast majority (92.6% ± 3.4% and 88.8% ± 2%, respectively) of FB-positive (FB+) nerve cells were TH+. TTX instillation caused a decrease in the number of FB+/TH+ neurons immunopositive to NPY (88.9% ± 5.3% in the control animals vs. 10.6% ± 5.3% in TTX-treated pigs) or VIP (1.7% ± 0.6% vs. 0%), and an increase in the number of FB+/TH+ neurons immunoreactive to SOM (8.8% ± 1.6% vs. 39% ± 12.8%), CB (1.8% ± 0.7% vs. 12.6% ± 2.7%), GAL (1.7% ± 0.8% vs. 10.9% ± 2.6%) or nNOS (0% vs. 1.1% ± 0.3%). The present study is the first to suggest that TTX modifies the chemical coding of CaMG neurons supplying the porcine urinary bladder. Full article

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Open AccessFeature PaperReview

Current Status of Marine-Derived Compounds as Warheads in Anti-Tumor Drug Candidates

by David J. Newman and Gordon M. Cragg

Mar. Drugs 2017, 15(4), 99; https://doi.org/10.3390/md15040099 - 29 Mar 2017

Cited by 61 | Viewed by 9195

Abstract

In this review, we have attempted to describe all of the antibody–drug conjugates using a marine-derived compound as the “warhead”, that are currently in clinical trials as listed in the current version of the NIH clinical trials database (clinicaltrials.gov). In searching this database, [...] Read more.

In this review, we have attempted to describe all of the antibody–drug conjugates using a marine-derived compound as the “warhead”, that are currently in clinical trials as listed in the current version of the NIH clinical trials database (clinicaltrials.gov). In searching this database, we used the beta-test version currently available, as it permitted more specific search parameters, since the regular version did not always find trials that had been completed in the past with some agents. We also added small discussion sections on candidates that are still at the preclinical stage, including a derivative of diazonamide that has an unusual interaction with tubulin (DZ-23840), which may also be a potential warhead in the future. Full article

(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)

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Open AccessFeature PaperArticle

Another Look at Pyrroloiminoquinone Alkaloids—Perspectives on Their Therapeutic Potential from Known Structures and Semisynthetic Analogues

by Sheng Lin, Erin P. McCauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote and Phillip Crews

Mar. Drugs 2017, 15(4), 98; https://doi.org/10.3390/md15040098 - 29 Mar 2017

Cited by 20 | Viewed by 5536

Abstract

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from [...] Read more.

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS² runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid carcinoma (PANC-1) cell line IC₅₀ data was obtained for 16 compounds and two therapeutic standards. These results along with data gleaned from the literature provided useful structure activity relationship conclusions. Three structural motifs proved to be important in maximizing potency against PANC-1: (i) conjugation within the core of the ABC-ring; (ii) the presence of a positive charge in the C-ring; and (iii) inclusion of a 4-ethyl phenol or 4-ethyl phenol acetate substituent off the B-ring. Two compounds, makaluvamine J (9) and 15-O-acetyl makaluvamine J (15), contained all three of these frameworks and exhibited the best potency with IC₅₀ values of 54 nM and 81 nM, respectively. These two most potent analogs were then tested against the OVCAR-5 cell line and the presence of the acetyl group increased the potency 14-fold from that of 9 whose IC₅₀ = 120 nM vs. that of 15 having IC₅₀ = 8.6 nM. Full article

(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)

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Open AccessArticle

Characterization and Potential Antitumor Activity of Polysaccharide from Gracilariopsis lemaneiformis

by Yani Kang, Zhi-Jiang Wang, Dongsheng Xie, Xue Sun, Wenge Yang, Xiaodong Zhao and Nianjun Xu

Mar. Drugs 2017, 15(4), 100; https://doi.org/10.3390/md15040100 - 29 Mar 2017

Cited by 74 | Viewed by 6178

Abstract

Substances with valuable antitumor properties have been identified in many marine algae, including an edible polysaccharide from the marine alga Gracilariopsis lemaneiformis (PGL). We previously reported transcriptome profiling data showing that PGL induced transcriptional alterations generate anti-lung cancer activity. To identify how PGL [...] Read more.

Substances with valuable antitumor properties have been identified in many marine algae, including an edible polysaccharide from the marine alga Gracilariopsis lemaneiformis (PGL). We previously reported transcriptome profiling data showing that PGL induced transcriptional alterations generate anti-lung cancer activity. To identify how PGL is detrimental to tumors, we purified PGL to characterize its chemical composition, molecular weight, and sugar and protein content and investigated its antitumor activity. We demonstrated that PGL exerted its antitumor activities by modulating cell viability, morphology, apoptosis, and the apoptosis-related Fas/FasL signaling pathway in the human lung cancer cell line A549, the gastric cancer cell line MKN28, and the mouse melanoma cell line B16. Our data provide the first evidence that PGL inhibits cell proliferation by inducing apoptosis, which is largely mediated by Fas/FasL in cancer cells, suggesting that PGL might be a novel therapeutic agent against cancer. Full article

(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)

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Open AccessArticle

Variation Quality and Kinetic Parameter of Commercial n-3 PUFA-Rich Oil during Oxidation via Rancimat

by Kai-Min Yang and Po-Yuan Chiang

Mar. Drugs 2017, 15(4), 97; https://doi.org/10.3390/md15040097 - 28 Mar 2017

Cited by 20 | Viewed by 5514

Abstract

Different biological sources of n-3 polyunsaturated fatty acids (n-3 PUFA) in mainstream commercial products include algae and fish. Lipid oxidation in n-3 PUFA-rich oil is the most important cause of its deterioration. We investigated the kinetic parameters of n [...] Read more.

Different biological sources of n-3 polyunsaturated fatty acids (n-3 PUFA) in mainstream commercial products include algae and fish. Lipid oxidation in n-3 PUFA-rich oil is the most important cause of its deterioration. We investigated the kinetic parameters of n-3 PUFA-rich oil during oxidation via Rancimat (at a temperature range of 70~100 °C). This was done on the basis of the Arrhenius equation, which indicates that the activation energies (Ea) for oxidative stability are 82.84–96.98 KJ/mol. The chemical substrates of different oxidative levels resulting from oxidation via Rancimat at 80 °C were evaluated. At the initiation of oxidation, the tocopherols in the oil degraded very quickly, resulting in diminished protection against further oxidation. Then, the degradation of the fatty acids with n-3 PUFA-rich oil was evident because of decreased levels of PUFA along with increased levels of saturated fatty acids (SFA). The quality deterioration from n-3 PUFA-rich oil at the various oxidative levels was analyzed chemometrically. The anisidine value (p-AV, r: 0.92) and total oxidation value (TOTOX, r: 0.91) exhibited a good linear relationship in a principal component analysis (PCA), while oxidative change and a significant quality change to the induction period (IP) were detected through an agglomerative hierarchical cluster (AHC) analysis. Full article

(This article belongs to the Special Issue Marine Lipids 2017)

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Open AccessReview

Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

by Anish Babu and Rajagopal Ramesh

Mar. Drugs 2017, 15(4), 96; https://doi.org/10.3390/md15040096 - 27 Mar 2017

Cited by 110 | Viewed by 10127

Abstract

Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has [...] Read more.

Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

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