Marine Drugs

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4181 KiB

Open AccessArticle

Pinnatifidenyne-Derived Ethynyl Oxirane Acetogenins from Laurencia viridis

by Adrián Morales-Amador, Caterina R. De Vera, Olivia Márquez-Fernández, Antonio Hernández Daranas, José M. Padrón, José J. Fernández, María L. Souto and Manuel Norte

Mar. Drugs 2018, 16(1), 5; https://doi.org/10.3390/md16010005 - 29 Dec 2017

Cited by 7 | Viewed by 5238

Abstract

Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C₁₅ acetogenin medium-ring ethers. Here, we described the isolation of three new C₁₅ acetogenins (3–5), and one truncated derivative (6) from [...] Read more.

Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C₁₅ acetogenin medium-ring ethers. Here, we described the isolation of three new C₁₅ acetogenins (3–5), and one truncated derivative (6) from Laurencia viridis collected on the Canary Islands. These compounds are interesting variations on the pinnatifidenyne structure that included the first examples of ethynyl oxirane derivatives (3–4). The structures were elucidated by extensive study of NMR (Nuclear Magnetic Resonance) data, J-based configuration analysis and DFT (Density Functional Theory) calculations. Their antiproliferative activity against six human solid tumor cell lines was evaluated. Full article

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

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5888 KiB

Open AccessFeature PaperArticle

Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer’s Disease Therapeutic Agents

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

Mar. Drugs 2017, 15(12), 366; https://doi.org/10.3390/md15120366 - 27 Nov 2017

Cited by 41 | Viewed by 9479

Abstract

Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity [...] Read more.

Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A–G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium, against various protein kinases involved in Alzheimer’s disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs. Full article

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

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1384 KiB

Open AccessArticle

Palladium-Catalyzed Dehydrogenative Coupling: An Efficient Synthetic Strategy for the Construction of the Quinoline Core

by Asier Carral-Menoyo, Verónica Ortiz-de-Elguea, Mikel Martinez-Nunes, Nuria Sotomayor and Esther Lete

Mar. Drugs 2017, 15(9), 276; https://doi.org/10.3390/md15090276 - 30 Aug 2017

Cited by 11 | Viewed by 5642

Abstract

Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields [...] Read more.

Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields via intramolecular C–H alkenylation reactions, by choosing the reaction conditions. This methodology provides a direct method for the construction of this type of quinoline through an efficient and atom economical procedure, and constitutes significant advance over the existing procedures that require preactivated reaction partners. Full article

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

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1231 KiB

Open AccessArticle

Bistratamides M and N, Oxazole-Thiazole Containing Cyclic Hexapeptides Isolated from Lissoclinum bistratum Interaction of Zinc (II) with Bistratamide K

by Carlos Urda, Rogelio Fernández, Jaime Rodríguez, Marta Pérez, Carlos Jiménez and Carmen Cuevas

Mar. Drugs 2017, 15(7), 209; https://doi.org/10.3390/md15070209 - 1 Jul 2017

Cited by 18 | Viewed by 5701

Abstract

Two novel oxazole-thiazole containing cyclic hexapeptides, bistratamides M (1) and N (2) have been isolated from the marine ascidian Lissoclinum bistratum (L. bistratum) collected in Raja Ampat (Papua Bar, Indonesia). The planar structure of 1 and 2 was assigned [...] Read more.

Two novel oxazole-thiazole containing cyclic hexapeptides, bistratamides M (1) and N (2) have been isolated from the marine ascidian Lissoclinum bistratum (L. bistratum) collected in Raja Ampat (Papua Bar, Indonesia). The planar structure of 1 and 2 was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of the Marfey’s and advanced Marfey’s methods after ozonolysis followed by acid-catalyzed hydrolysis. The interaction between zinc (II) and the naturally known bistratamide K (3), a cyclic hexapeptide isolated from a different specimen of Lissoclinum bistratum, was monitored by ¹H and ¹³C NMR. The results obtained are consistent with the proposal that these peptides are biosynthesized for binding to metal ions. Compounds 1 and 2 display moderate cytotoxicity against four human tumor cell lines with GI₅₀ values in the micromolar range. Full article

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

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1342 KiB

Open AccessArticle

The Roles of Spinochromes in Four Shallow Water Tropical Sea Urchins and Their Potential as Bioactive Pharmacological Agents

by Lola Brasseur, Elise Hennebert, Laurence Fievez, Guillaume Caulier, Fabrice Bureau, Lionel Tafforeau, Patrick Flammang, Pascal Gerbaux and Igor Eeckhaut

Mar. Drugs 2017, 15(6), 179; https://doi.org/10.3390/md15060179 - 16 Jun 2017

Cited by 49 | Viewed by 6331

Abstract

Spinochromes are principally known to be involved in sea urchin pigmentation as well as for their potentially interesting pharmacological properties. To assess their biological role in sea urchin physiology, experiments are undertaken on crude extracts from four species and on four isolated spinochromes [...] Read more.

Spinochromes are principally known to be involved in sea urchin pigmentation as well as for their potentially interesting pharmacological properties. To assess their biological role in sea urchin physiology, experiments are undertaken on crude extracts from four species and on four isolated spinochromes in order to test their antibacterial, antioxidant, inflammatory and cytotoxic activities. First, the antibacterial assays show that the use of crude extracts as representatives of antibacterial effects of spinochromes are inaccurate. The assays on purified spinochromes showed a decrease in the growth of four strains with an intensity depending on the spinochromes/bacteria system, revealing the participation of spinochromes in the defense system against microorganisms. Secondly, in the 2,2-diphenyl-1-picrylhydrazyl antioxidant assays, spinochromes show an enhanced activity compared to the positive control. This latter observation suggests their involvement in ultraviolet radiation protection. Third, spinochromes present a pro-inflammatory effect on lipopolysaccharide-stimulated macrophages, highlighting their possible implication in the sea urchin immune system. Finally, cytotoxicity assays based on Trypan blue exclusion, performed in view of their possible future applications as drugs, show a weak cytotoxicity of these compounds against human cells. In conclusion, all results confirm the implication of spinochromes in sea urchin defense mechanisms against their external environment and reveal their potential for pharmacological and agronomical industries. Full article

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

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1638 KiB

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 5496

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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Review

Jump to: Research

32 pages, 7672 KiB

Open AccessReview

Marine Alkylpurines: A Promising Group of Bioactive Marine Natural Products

by Pablo A. García, Elena Valles, David Díez and María-Ángeles Castro

Mar. Drugs 2018, 16(1), 6; https://doi.org/10.3390/md16010006 - 1 Jan 2018

Cited by 16 | Viewed by 6986

Abstract

Marine secondary metabolites with a purine motif in their structure are presented in this review. The alkylpurines are grouped according to the size of the alkyl substituents and their location on the purine ring. Aspects related to the marine source, chemical structure and [...] Read more.

Marine secondary metabolites with a purine motif in their structure are presented in this review. The alkylpurines are grouped according to the size of the alkyl substituents and their location on the purine ring. Aspects related to the marine source, chemical structure and biological properties are considered together with synthetic approaches towards the natural products and bioactive analogues. This review contributes to studies of structure–activity relationships for these metabolites and highlights the potential of the sea as a source of new lead compounds in diverse therapeutic fields. Full article

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

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6814 KiB

Open AccessFeature PaperReview

The Oxepane Motif in Marine Drugs

by Héctor Barbero, Carlos Díez-Poza and Asunción Barbero

Mar. Drugs 2017, 15(11), 361; https://doi.org/10.3390/md15110361 - 15 Nov 2017

Cited by 30 | Viewed by 9488

Abstract

Oceans have shown to be a remarkable source of natural products. The biological properties of many of these compounds have helped to produce great advances in medicinal chemistry. Within them, marine natural products containing an oxepanyl ring are present in a great variety [...] Read more.

Oceans have shown to be a remarkable source of natural products. The biological properties of many of these compounds have helped to produce great advances in medicinal chemistry. Within them, marine natural products containing an oxepanyl ring are present in a great variety of algae, sponges, fungus and corals and show very important biological activities, many of them possessing remarkable cytotoxic properties against a wide range of cancer cell lines. Their rich chemical structures have attracted the attention of many researchers who have reported interesting synthetic approaches to these targets. This review covers the most prominent examples of these types of compounds, focusing the discussion on the isolation, structure determination, medicinal properties and total synthesis of these products. Full article

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

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