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1.
Chin J Nat Med ; 18(11): 844-849, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33308606

RESUMEN

Four new polyhydroxylated steroids plaksterols A-D (1-4), together with two known related steroids ergost-7,9(11),22-trien-3ß,5α,6α-triol (5) and ergosta-6ß-methoxy-7,22-diene-3ß,5α-diol (6), were isolated from methanol extract of the South China Sea marine sponge Plakortis sp. Their structures were identified by spectroscopic analysis, including NMR, MS, and IR. The cytotoxicity of the polyhydroxylated steroids were evaluated, and compound 6 showed moderate inhibitory activities against K562, HL-60 and BEL-7402 cells.

2.
Mol Ecol Resour ; 2020 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-32866335

RESUMEN

Plasmid transfers among bacterial populations can directly influence the ecological adaptation of these populations and their interactions with host species and environment. In this study, we developed a selective multiply-primed rolling circle amplification (smRCA) approach to enrich and characterize circular plasmid DNA from sponge microbial symbionts via high-throughput sequencing (HTS). DNA (plasmid and total community DNA) obtained from sponge (Cinachyrella sp.) samples and a bacterial symbiont (Vibrio sp. CyArs1) isolated from the same sponge species (carrying unknown plasmids) were used to develop and validate our methodology. The smRCA was performed during 16 hr with 141 plasmid-specific primers covering all known circular plasmid groups. The amplified products were purified and subjected to a reamplification with random hexamer primers (2 hr) and then sequenced using Illumina MiSeq. The developed method resulted in the successful amplification and characterization of the sponge plasmidome and allowed us to detect plasmids associated with the bacterial symbiont Vibrio sp. CyArs1 in the sponge host. In addition to this, a large number of small (<2 kbp) and cryptic plasmids were also amplified in sponge samples. Functional analysis identified proteins involved in the control of plasmid partitioning, maintenance and replication. However, most plasmids contained unknown genes, which could potentially serve as a resource of unknown genetic information and novel replication systems. Overall, our results indicate that the smRCA-HTS approach developed here was able to selectively enrich and characterize plasmids from bacterial isolates and sponge host microbial communities, including plasmids larger than 20 kbp.

3.
Microorganisms ; 8(9)2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32825344

RESUMEN

Aging research aims at developing therapies that delay normal aging processes and some related pathologies. Recently, many compounds and extracts from natural products have been shown to slow aging and/or extend lifespan. Marine sponges and their associated microorganisms have been found to produce a wide variety of bioactive secondary metabolites; however, those from the Southwest of the Indian Ocean are much less studied, especially regarding anti-aging activities. In this study, the microbial diversity of the marine sponge Scopalina hapalia was investigated by metagenomic analysis. Twenty-six bacterial and two archaeal phyla were recovered from the sponge, of which the Proteobacteria phylum was the most abundant. In addition, 30 isolates from S. hapalia were selected and cultivated for identification and secondary metabolites production. The selected isolates were affiliated to the genera Bacillus, Micromonospora, Rhodoccocus, Salinispora, Aspergillus, Chaetomium, Nigrospora and unidentified genera related to the family Thermoactinomycetaceae. Crude extracts from selected microbial cultures were found to be active against seven clinically relevant targets (elastase, tyrosinase, catalase, sirtuin 1, Cyclin-dependent kinase 7 (CDK7), Fyn kinase and proteasome). These results highlight the potential of microorganisms associated with a marine sponge from Mayotte to produce anti-aging compounds. Future work will focus on the isolation and the characterization of bioactive compounds.

4.
Mar Drugs ; 18(7)2020 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-32635268

RESUMEN

Chemical study of the CH2Cl2-MeOH (1:1) extract from the sponge Haliclona sp. collected in Mayotte highlighted three new long-chain highly oxygenated polyacetylenes, osirisynes G-I (1-3) together with the known osirisynes A (4), B (5), and E (6). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS and MS/MS data. All compounds were evaluated on catalase and sirtuin 1 activation and on CDK7, proteasome, Fyn kinase, tyrosinase, and elastase inhibition. Five compounds (1; 3-6) inhibited proteasome kinase and two compounds (5-6) inhibited CDK7 and Fyn kinase. Osirisyne B (5) was the most active compound with IC50 on FYNB kinase, CDK7 kinase, and proteasome inhibition of 18.44 µM, 9.13 µM, and 0.26 µM, respectively.

5.
ACS Omega ; 5(21): 12398-12408, 2020 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-32548424

RESUMEN

Despite their high therapeutic potential, only a limited number of approved drugs originate from marine natural products. A possible reason for this is their broad metabolic variability related to the environment, which can cause reproducibility issues. Consequently, a further understanding of environmental factors influencing the production of metabolites is required. Giant barrel sponges, Xestospongia spp., are a source of many new compounds and are found in a broad geographical range. In this study, the relationship between the metabolome and the geographical location of sponges within the genus Xestospongia spp. was investigated. One hundred and thirty-nine specimens of giant barrel sponges (Xestospongia spp.) collected in four locations, Martinique, Curaçao, Taiwan, and Tanzania, were studied using a multiplatform metabolomics methodology (nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry). A clear grouping of the collected samples according to their location was shown. Metabolomics analysis revealed that sterols and various fatty acids, including polyoxygenated and brominated derivatives, were related to the differences in locations. To explore the relationship between observed metabolic changes and their bioactivity, antibacterial activity was assessed against Escherichia coli and Staphylococcus aureus. The activity was found to correlate with brominated fatty acids. These were isolated and identified as (9E,17E)-18-bromooctadeca-9,17-dien-5,7,15-triynoic acid (1), xestospongic acid (2), (7E,13E,15Z)-14,16-dibromohexadeca-7,13,15-trien-5-ynoic acid (3), and two previously unreported compounds.

6.
J Nat Prod ; 83(2): 516-523, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-31990554

RESUMEN

Granulosane A (1), a new C27 bishomoscalarane sesterterpenoid with a rare 6/6/6/8 tetracyclic skeleton, together with eight additional new C27 bishomoscalarane sesterterpenes (2, 8-14) and five new C26 20,24-bishomo-25-norscalarane sesterterpenes (3-7), were isolated from the marine sponge Dysidea granulosa collected in the South China Sea. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculation methods. Compound 4 showed antiproliferative activities against two cancer cell lines.

7.
Nat Prod Res ; 34(6): 790-796, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30445862

RESUMEN

A new dolabellane diterpenoid, clavirolide H (1), together with eleven known compounds, including two dolabellane diterpenoid (2 and 3), a rare cavernosine-type C17 γ-lactone terpenoid (4), a diketopiperazine (5) and seven sterols (6-12), were isolated from the Xisha sponge Fascaplysinopsis reticulata. Their structures were elucidated by extensive spectroscopic analysis, and the four types of compounds of the above isolates were reported from the genus Fascaplysinopsis for the first time. Selected compounds 1, 4-6 and 9-12 were evaluated for cytotoxic activities against K562, HL-60, Hela, HCT-116, A549, L-02 and BEL-7402 cell lines. Compounds 4-6 and 10-12 showed potent cytotoxicitives against HL-60 with IC50 values ranging from 8.8 to 12.4 µM. Compounds 4 and 5 exhibited weak cytotoxic activities against HeLa with IC50 of 20.7 and 27.4 µM, and 5 also has moderate cytotoxicity against HCT-116 with IC50 of 16.3 µM.[Figure: see text].


Asunto(s)
Antineoplásicos/aislamiento & purificación , Citotoxinas/aislamiento & purificación , Poríferos/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular , Línea Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacología , Dicetopiperazinas/aislamiento & purificación , Diterpenos/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Esteroles/aislamiento & purificación , Terpenos/aislamiento & purificación
8.
Org Lett ; 21(23): 9483-9486, 2019 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-31746608

RESUMEN

One new dimeric bromopyrrole alkaloid, agelanemoechine, with an unprecedented imidazo [1,5-a] azepin nucleus together with one known dimeric bromopyrrole alkaloid sceptrin were isolated from the marine sponge Agelas nemoechinata. The structure elucidation and absolute configuration assignments were determined by extensive spectroscopic analyses and the comparison of experimental and calculated ECD. Agelanemoechine showed strong pro-angiogenic activity in zebrafish.


Asunto(s)
Agelas , Alcaloides/química , Alcaloides/farmacología , Inductores de la Angiogénesis/química , Inductores de la Angiogénesis/farmacología , Pirroles/química , Pirroles/farmacología , Animales , Animales Modificados Genéticamente , China , Estructura Molecular , Océanos y Mares , Ftalazinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Pez Cebra
9.
Nat Prod Res ; : 1-6, 2019 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-31631697

RESUMEN

A new sesquiterpene, (+)-19-methylaminoavarone (1), together with six known compounds (2-7), were isolated from the Xisha Islands marine sponge Dysidea sp. The structures were elucidated based on their spectroscopic data. We revised the carbon spectrum data of the compound 2. The absolute configurations of compounds 1 and 2 were further confirmed by electronic circular dichroism (ECD) analysis. Compounds 1-3 and 5-7 showed potent cytotoxic activity against several human cancer cell lines.

10.
Nat Commun ; 10(1): 1644, 2019 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-30967538

RESUMEN

Much recent marine microbial research has focused on sponges, but very little is known about how the sponge microbiome fits in the greater coral reef microbial metacommunity. Here, we present an extensive survey of the prokaryote communities of a wide range of biotopes from Indo-Pacific coral reef environments. We find a large variation in operational taxonomic unit (OTU) richness, with algae, chitons, stony corals and sea cucumbers housing the most diverse prokaryote communities. These biotopes share a higher percentage and number of OTUs with sediment and are particularly enriched in members of the phylum Planctomycetes. Despite having lower OTU richness, sponges share the greatest percentage (>90%) of OTUs with >100 sequences with the environment (sediment and/or seawater) although there is considerable variation among sponge species. Our results, furthermore, highlight that prokaryote microorganisms are shared among multiple coral reef biotopes, and that, although compositionally distinct, the sponge prokaryote community does not appear to be as sponge-specific as previously thought.


Asunto(s)
Organismos Acuáticos/aislamiento & purificación , Bacterias/aislamiento & purificación , Arrecifes de Coral , Microbiota , Poríferos/microbiología , Animales , Organismos Acuáticos/genética , Bacterias/genética , ADN Bacteriano/aislamiento & purificación , Sedimentos Geológicos/microbiología , ARN Ribosómico 16S/genética , Agua de Mar/microbiología , Taiwán , Tailandia
11.
Bioorg Med Chem Lett ; 29(1): 8-10, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30455150

RESUMEN

A new halicyclamine derivative, tetradehydrohalicyclamine B (1), was isolated from the marine sponge Acanthostrongylophora ingens, along with halicyclamine B (2) as proteasome inhibitors. Compound 1 is the second example found to have a pyridinium ring in the halicyclamine family. Although the relative configuration of 2 was previously determined by X-ray crystallographic analysis, here we determined the absolute configuration of 2 by ECD experiment. Compounds 1 and 2 inhibited the constitutive proteasome as well as the immunoproteasome. The inhibitory activities of 2 were 4- to 10-fold more potent than those of 1.


Asunto(s)
Depsipéptidos/farmacología , Poríferos/química , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma/farmacología , Animales , Cristalografía por Rayos X , Depsipéptidos/química , Depsipéptidos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteasoma/química , Inhibidores de Proteasoma/aislamiento & purificación , Relación Estructura-Actividad
12.
Zootaxa ; 4500(1): 43-58, 2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30486076

RESUMEN

Sponges of the order Haplosclerida are often abundant and characteristic components of Indo-Pacific reefs, but are often misidentified, because of the lack of clear distinctive morphological characters. Neopetrosia exigua is an example of a haplosclerid sponge that is very common in Indonesian shallow coral reef environments but bears several different names. In the present study we investigated type material of several Indo-Pacific Neopetrosia species with a similar morphology and examined freshly collected specimen materials including specimens that are deposited at several institutions. In addition, we used molecular phylogenetic methods for assisting the morphological examinations. We conclude that the true identity of Neopetrosia exigua should be Neopetrosia chaliniformis. Likewise, N. exigua and N. pacifica should be considered as junior synonyms of N. chaliniformis. In conclusion, we advocate that molecular barcoding could significantly aid on sponge species' delimitation that possess limited morphological characters.


Asunto(s)
Arrecifes de Coral , Filogenia , Animales , Indonesia , Poríferos , Agua
13.
PeerJ ; 6: e5586, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30280018

RESUMEN

Correct identification and classification of sponges is challenging due to ambiguous or misleading morphological features. A particular case is a blue keratose sponge occasionally referred to as the "Blue Photo Sponge" among aquarists, which appears frequently (and in several cases unintended) in private aquaria. This spicule-less species, occasionally specified as Collospongia auris Bergquist, Cambie & Kernan 1990, not only displays a high phenotypic plasticity in growth form and colour, it also proliferates in aquacultures under standard conditions unlike most other sponges. Therefore, this species is regarded as a pest for most aquarists. In turn, the ease of cultivation and propagation in aquacultures qualifies this species as a model organism for a wide array of scientific applications. For these purposes, correct identification and classification are indispensable. We reconstructed ribosomal gene trees and determined this species as Lendenfeldia chondrodes (De Laubenfels, 1954) (Phyllospongiinae), distant to Collospongia auris, and corroborated by skeletal features. Additionally, the resulting phylogeny corroborated major shortcomings of the current Phyllospongiinae classification-its consequences are discussed.

14.
Zootaxa ; 4426(1): 1-160, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-30313293

RESUMEN

Past taxonomic studies of Western Indian Ocean and Red Sea Calcarea have been few and sporadic (e.g. Schuffner 1877, Jenkin 1908, Row 1909, Dendy 1913, 1916, Voigt et al. 2017, 2018). Nevertheless, approximately 70 species are known from these studies for the considered region, but the descriptions of the older records often lack sufficient details for reliable identification. We studied the Western Indian Ocean Calcarea collection kept in the Naturalis Biodiversity Center. Available specimens numbered 145, collected in the Red Sea, Seychelles, Maldives, Mayotte and Rodrigues, in addition to incidental samples from Oman, the Lakshadweep Islands, the Mozambique Channel, and Eastern South Africa. Using a combination of techniques (in situ and 'on deck' photography, detailed field notes, light microscopic studies and measurements, SEM microscopy, and selected DNA sequencing) we identified 45 species, divided over the two main classes Calcinea (24 spp.) and Calcaronea (21 spp.). Not all species could be definitely assigned to an already described or a new species, as seven remained qualified as 'spec.' or 'aff.' for reasons of insufficient material or lack of details of in situ habitus. Sixteen species appeared to be new to science: Borojevia voigti sp.nov., Borojevia tubulata sp.nov., Borojevia pirella sp.nov., Clathrina rodriguesensis sp.nov., Clathrina maremeccae sp.nov., Clathrina repens sp.nov., Leucascus schleyeri sp.nov., Leucetta sulcata sp.nov., Ute insulagemmae sp.nov., Leucandra pilula sp.nov., Leucandra mozambiquensis sp.nov., Grantessa woerheidei sp.nov., Sycettusa hirsutissima sp.nov., Vosmaeropsis glebula sp.nov., Paraleucilla erpenbecki sp.nov., and Kebira tetractinifera sp.nov. For a selection of the identified species from the Western Indian Ocean and the Red Sea (30 spp.), as well as from Indonesian material (22 spp.) published previously (see Van Soest De Voogd 2015) we obtained sequences of the partial 28S gene of nuclear rDNA (C2-D2 region, cf. Voigt Wörheide 2016). The sequences of the Western Indian Ocean and Red Sea species were used to assign these to genera and families based on a phylogenetic analysis using MEGA pack vs. 06.6 for Mac of the available dataset. The Indonesian sequences supplemented by partial 28S sequences taken from the Sponge Barcode Project website and the NCBI website were included in the phylogenetic analysis to confirm the assignments. The results were compared and discussed with additional information on regional Calcarea not represented in our material. The latter chapter yielded the discovery of a preoccupied name leading to Sycon oscari nom.nov. for a species described from Mauritius.


Asunto(s)
Filogenia , Poríferos , Animales , Océano Índico , Islas del Oceano Índico , Medio Oriente
15.
Zootaxa ; 4466(1): 1-2, 2018 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-30313433

RESUMEN

N/A.

16.
Microb Ecol ; 76(3): 610-624, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29470608

RESUMEN

Marine lakes are small bodies of landlocked seawater that are isolated from the open sea and have been shown to house numerous rare and unique taxa. The environmental conditions of the lakes are also characterised by lower pH and salinity and higher temperatures than generally found in the open sea. In the present study, we used a 16S rRNA gene barcoded pyrosequencing approach and a predictive metagenomic approach (PICRUSt) to examine bacterial composition and function in three distinct biotopes (sediment, water and the sponge species Biemna fortis) in three habitats (two marine lakes and the open sea) of the Berau reef system, Indonesia. Both biotope and habitat were significant predictors of higher taxon abundance and compositional variation. Most of the variation in operational taxonomic unit (OTU) composition was related to the biotope (42% for biotope alone versus 9% for habitat alone and 15% combined). Most OTUs were also restricted to a single biotope (1047 for B. fortis, 6120 for sediment and 471 for water). Only 98 OTUs were shared across all three biotopes. Bacterial communities from B. fortis, sediment and water samples were, however, also distinct in marine lake and open sea habitats. This was evident in the abundance of higher bacterial taxa. For example, the phylum Cyanobacteria was significantly more abundant in samples from marine lakes than from the open sea. This difference was most pronounced in the sponge B. fortis. In line with the compositional differences, there were pronounced differences in predicted relative gene count abundance among biotopes and habitats. Of particular interest was the predicted enrichment in B. fortis from the marine lakes for pathways including DNA replication and repair and the glutathione metabolism. This may facilitate adaptation of host and microbes to life in 'stressful' low pH, low salinity and/or high temperature environments such as those encountered in marine lakes.


Asunto(s)
Bacterias/aislamiento & purificación , Sedimentos Geológicos/microbiología , Lagos/microbiología , Poríferos/microbiología , Agua de Mar/microbiología , Animales , Archaea , Bacterias/clasificación , Bacterias/genética , Biodiversidad , Arrecifes de Coral , Ecosistema , Indonesia , Filogenia
17.
Chem Biodivers ; 15(2)2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29194948

RESUMEN

Chemical examination of the bright yellow sponge Leucetta chagosensis resulted in the isolation of three new imidazole-based alkaloid complexes namely chagosendines A - C (1 - 3), together with known analogues pyronaamidine, naamidine J, and naamine C. Their structures were determined on the basis of extensive spectroscopic (IR, MS, NMR, and single-crystal X-ray diffraction) analysis in association with the chemical conversion. The isolated alkaloids together with three synthesized new homodimer complexes were evaluated for the cytotoxic activities against a panel of tumor cell lines. The copper complexes of imidazole alkaloids 2 and 3, as found from nature for the first time, exerted selective and remarkable activities against the tumor cell lines K562, HepG2, and HeLa.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Complejos de Coordinación/farmacología , Imidazoles/farmacología , Poríferos/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/química , Complejos de Coordinación/aislamiento & purificación , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Células Hep G2 , Humanos , Imidazoles/química , Imidazoles/aislamiento & purificación , Células K562 , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad
18.
FEMS Microbiol Ecol ; 94(2)2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29228244

RESUMEN

Certain sponge species are difficult to identify using classical taxonomic characters, and other techniques are often necessary. Here we used 454-pyrosequencing of the 16S rRNA gene to investigate bacterial and archaeal communities of two distinct Cinachyrella morphospecies collected from two Indonesian marine lakes with differing degrees of connection to the surrounding sea. Our main goal was to assess whether these morphospecies hosted distinct bacterial and archaeal communities and to what extent these differed from those found in lake water. A recently developed bioinformatic tool (PICRUSt) was used to predict metagenomic gene content of the studied communities. Compositionally, sponge samples clustered according to morphospecies as opposed to marine lake indicating that each morphospecies hosted distinct bacterial and archaeal communities. There were, however, also differences in higher taxon abundance among lakes. In the less connected lake, for example, both Cinachyrella morphospecies had higher levels of the order Synechococcales. With respect to metabolic gene content, although there were pronounced differences in predicted enrichment between both morphospecies, both were putatively enriched for KOs involved in pathways related to stress response, energy metabolism, environmental information processing and the production of secondary metabolites compared to prokaryote communities in water. These morphospecies may thus prove to be interesting sources of novel compounds of potential pharmaceutical and/or biotechnological importance.


Asunto(s)
Archaea/clasificación , Bacterias/clasificación , Microbiota/genética , Poríferos/microbiología , Animales , Archaea/genética , Bacterias/genética , Biodiversidad , Indonesia , Lagos/microbiología , Metagenómica , Filogenia , Poríferos/genética , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
19.
Mar Drugs ; 17(1)2018 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-30597876

RESUMEN

Chemical investigation of MeOH extract of a South China Sea sponge Cacospongia sp. yielded 15 terpenoids belonging to three different skeleton-types, including the unusual C17 γ-lactone norditerpenoids (1⁻3), the rare C21 pyridine meroterpenoid (7), and the notable C25 manoalide-type sesterterpenoids (4⁻6, 8⁻10). Compounds 1⁻5 were initially obtained as enantiomers, and were further separated to be optically pure compounds (1a, 1b, 2a, 2b, 3a-r, 3b-r, 4a, 4b, 5a and 5b) by chiral HPLC, with a LiAlH4 reduction aid for 3. Compounds 3a/3b (a pair of inseparable enantiomers), 4a, 5a, 6, and 7 were identified as new compounds, while 1a/1b and 2a/2b were obtained from a natural source and were determined for their absolute configurations for the first time. This is also the first time to encounter enantiomers of the well-known manoalide-type sesterterpenoids from nature. The structures with absolute configurations of the new compounds were unambiguously determined by comprehensive methods including HR-ESI-MS and NMR data analysis, optical rotation comparison, experimental and calculated electronic circular dichroism (ECD), and Mo2(OAc)4 induced circular dichroism (ICD) methods. The cytotoxicity of the isolates against selected human tumor cell lines was evaluated, however, the tested compounds showed no activity against selected cell lines.


Asunto(s)
Poríferos/química , Terpenos/química , Animales , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión/métodos , Dicroismo Circular/métodos , Diterpenos/química , Humanos , Espectroscopía de Resonancia Magnética/métodos , Rotación Óptica , Estereoisomerismo
20.
Antiviral Res ; 145: 136-145, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28827084

RESUMEN

The currently available antiviral agents for chronic infection with hepatitis B virus (HBV) are pegylated interferon-α and nucleoside/nucleotide analogues, although it has been difficult to completely eliminate covalently closed circular DNA (cccDNA) from patients. To identify an antiviral compound targeting HBV core promoter, 15 terpenes originating from marine organisms were screened using a cell line expressing firefly luciferase under the control of the HBV core promoter. Metachromin A, which is a merosesquiterpene isolated from the marine sponge Dactylospongia metachromia, inhibited the viral promoter activity at the highest level among the tested compounds, and suppressed HBV production with an EC50 value of 0.8 µM regardless of interferon signaling and cytotoxicity. The analysis on the structure-activity relationship revealed that the hydroquinone moiety, and the double bonds at carbon numbers-5 and -9 in metachromin A are crucial for anti-HBV activity. Furthermore, metachromin A reduced the protein level but not the RNA level of hepatic nuclear factor 4α, which mainly upregulates the activities of enhancer I/X promoter and enhancer II/core promoter. These results suggest that metachromin A can inhibit HBV production via impairment of the viral promoter activity. Antiviral agents targeting the viral promoter may ameliorate HBV-related disorders regardless of remaining cccDNA.


Asunto(s)
Antivirales/química , Antivirales/farmacología , Virus de la Hepatitis B/efectos de los fármacos , Regiones Promotoras Genéticas/efectos de los fármacos , Sesquiterpenos/farmacología , Antivirales/aislamiento & purificación , Línea Celular , Replicación del ADN/efectos de los fármacos , ADN Viral/efectos de los fármacos , Descubrimiento de Drogas , Células Hep G2 , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Sesquiterpenos/administración & dosificación , Relación Estructura-Actividad , Terpenos/química , Terpenos/aislamiento & purificación , Terpenos/farmacología , Replicación Viral/efectos de los fármacos
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