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1.
Zootaxa ; 5297(1): 48-60, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37518810

RESUMO

Ophlitaspongia (?) arbuscula Row, 1911 and Ophlitaspongia (?) horrida Row, 1911 from the type locality in the Red Sea, have been re-described based on the type and fresh material from the Red Sea, Egypt. New specimens were used to illustrate the variation within the species. Examination of the type and fresh material indicates both species are unlikely to belong to the genus Ophlitaspongia, due to the possession of echinating (acantho)styles. The presence of a reticulate skeleton indicates Clathria (Clathria) Schmidt, 1862, is the most likely generic assignment for both species.


Assuntos
Poríferos , Animais , Oceano Índico , Poríferos/classificação
2.
Nature ; 618(7963): 110-117, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37198475

RESUMO

A central question in evolutionary biology is whether sponges or ctenophores (comb jellies) are the sister group to all other animals. These alternative phylogenetic hypotheses imply different scenarios for the evolution of complex neural systems and other animal-specific traits1-6. Conventional phylogenetic approaches based on morphological characters and increasingly extensive gene sequence collections have not been able to definitively answer this question7-11. Here we develop chromosome-scale gene linkage, also known as synteny, as a phylogenetic character for resolving this question12. We report new chromosome-scale genomes for a ctenophore and two marine sponges, and for three unicellular relatives of animals (a choanoflagellate, a filasterean amoeba and an ichthyosporean) that serve as outgroups for phylogenetic analysis. We find ancient syntenies that are conserved between animals and their close unicellular relatives. Ctenophores and unicellular eukaryotes share ancestral metazoan patterns, whereas sponges, bilaterians, and cnidarians share derived chromosomal rearrangements. Conserved syntenic characters unite sponges with bilaterians, cnidarians, and placozoans in a monophyletic clade to the exclusion of ctenophores, placing ctenophores as the sister group to all other animals. The patterns of synteny shared by sponges, bilaterians, and cnidarians are the result of rare and irreversible chromosome fusion-and-mixing events that provide robust and unambiguous phylogenetic support for the ctenophore-sister hypothesis. These findings provide a new framework for resolving deep, recalcitrant phylogenetic problems and have implications for our understanding of animal evolution.


Assuntos
Ctenóforos , Filogenia , Animais , Ctenóforos/classificação , Ctenóforos/genética , Genoma/genética , Poríferos/classificação , Poríferos/genética , Sintenia/genética
3.
Zootaxa ; 5162(1): 87-96, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-36095521

RESUMO

We describe a new deep-sea sponge species, Fibulia occiensis sp. nov., from the Central Indian Ocean Ridge (CIOR) at Rodrigues Triple Junction (RTJ), of the family Dendoricellidae Hentschel, 1923. Two sponge specimens were collected between 19822079 m depth using a benthic sledge in the 25 South Oceanic Core Complex (OCC) region. The megabenthic fauna was collected to establish a baseline of environmental and benthic ecological data. This data will be handy in assessing the impact of sulfide mining in the near future. Fibulia occiensis sp. nov. is fragile and stalked, has a single type of oxea, and no sigma. The new species is different from the congeneric Fibulia species by its larger oxeas and the strongly curved isochelae.


Assuntos
Poríferos , Animais , Oceano Índico , Poríferos/classificação
4.
Mar Drugs ; 20(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35323489

RESUMO

Species misidentification in the field of natural products is an acknowledged problem. These errors are especially widespread in sponge studies, albeit rarely assessed and documented. As a case study, we aim to revisit reports of isomalabaricane triterpenes, isolated from four demosponge genera: Jaspis, Geodia, Stelletta and Rhabdastrella. From a total of 44 articles (1981-2022), 27 unique vouchers were listed, 21 of which were accessed and re-examined here: 11 (52.4%) of these were misidentified. Overall, 65.9% of the studies published an incorrect species name: previously identified Jaspis and Stelletta species were all in fact Rhabdastrella globostellata. We conclude that isomalabaricane triterpenes were isolated from only two Rhabdastrella species and possibly one Geodia species. In addition to shedding a new light on the distribution of isomalabaricane triterpenes, this study is an opportunity to highlight the crucial importance of vouchers in natural product studies. Doing so, we discuss the impact of species misidentification and poor accessibility of vouchers in the field of sponge natural products. We advocate for stricter voucher guidelines in natural product journals and propose a common protocol of good practice, in the hope of reducing misidentifications in sponge studies, ensure reproducibility of studies, and facilitate follow-up work on the original material.


Assuntos
Produtos Biológicos , Poríferos , Triterpenos , Animais , Produtos Biológicos/classificação , Produtos Biológicos/isolamento & purificação , Poríferos/química , Poríferos/classificação , Reprodutibilidade dos Testes , Triterpenos/classificação , Triterpenos/isolamento & purificação
5.
Sci Rep ; 12(1): 1307, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35079031

RESUMO

Upon injury, the homeostatic balance that ensures tissue function is disrupted. Wound-induced signaling triggers the recovery of tissue integrity and offers a context to understand the molecular mechanisms for restoring tissue homeostasis upon disturbances. Marine sessile animals are particularly vulnerable to chronic wounds caused by grazers that can compromise prey's health. Yet, in comparison to other stressors like warming or acidification, we know little on how marine animals respond to grazing. Marine sponges (Phylum Porifera) are among the earliest-diverging animals and play key roles in the ecosystem; but they remain largely understudied. Here, we investigated the transcriptomic responses to injury caused by a specialist spongivorous opisthobranch (i.e., grazing treatment) or by clipping with a scalpel (i.e., mechanical damage treatment), in comparison to control sponges. We collected samples 3 h, 1 d, and 6 d post-treatment for differential gene expression analysis on RNA-seq data. Both grazing and mechanical damage activated a similar transcriptomic response, including a clotting-like cascade (e.g., with genes annotated as transglutaminases, metalloproteases, and integrins), calcium signaling, and Wnt and mitogen-activated protein kinase signaling pathways. Wound-induced gene expression signature in sponges resembles the initial steps of whole-body regeneration in other animals. Also, the set of genes responding to wounding in sponges included putative orthologs of cancer-related human genes. Further insights can be gained from taking sponge wound healing as an experimental system to understand how ancient genes and regulatory networks determine healthy animal tissues.


Assuntos
Neoplasias/genética , Poríferos/genética , Transdução de Sinais/genética , Transcriptoma/genética , Cicatrização/genética , Animais , Regulação para Baixo/genética , Ecossistema , Redes Reguladoras de Genes , Humanos , Modelos Animais , Filogenia , Poríferos/classificação , Mapas de Interação de Proteínas/genética , RNA-Seq/métodos , Regulação para Cima/genética
6.
Sci Rep ; 11(1): 21151, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34707182

RESUMO

Although the Mediterranean Sea covers approximately a 0.7% of the world's ocean area, it represents a major reservoir of marine and coastal biodiversity. Among marine organisms, sponges (Porifera) are a key component of the deep-sea benthos, widely recognized as the dominant taxon in terms of species richness, spatial coverage, and biomass. Sponges are evolutionarily ancient, sessile filter-feeders that harbor a largely diverse microbial community within their internal mesohyl matrix. In the present work, we firstly aimed at exploring the biodiversity of marine sponges from four different areas of the Mediterranean: Faro Lake in Sicily and "Porto Paone", "Secca delle fumose", "Punta San Pancrazio" in the Gulf of Naples. Eight sponge species were collected from these sites and identified by morphological analysis and amplification of several conserved molecular markers (18S and 28S RNA ribosomal genes, mitochondrial cytochrome oxidase subunit 1 and internal transcribed spacer). In order to analyze the bacterial diversity of symbiotic communities among these different sampling sites, we also performed a metataxonomic analysis through an Illumina MiSeq platform, identifying more than 1500 bacterial taxa. Amplicon Sequence Variants (ASVs) analysis revealed a great variability of the host-specific microbial communities. Our data highlight the occurrence of dominant and locally enriched microbes in the Mediterranean, together with the biotechnological potential of these sponges and their associated bacteria as sources of bioactive natural compounds.


Assuntos
Microbiota , Poríferos/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/patogenicidade , Código de Barras de DNA Taxonômico , Mar Mediterrâneo , Poríferos/classificação , Poríferos/genética , Simbiose
7.
Mar Drugs ; 19(8)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34436287

RESUMO

Marine sponges are the most prolific marine sources for discovery of novel bioactive compounds. Sponge secondary metabolites are sought-after for their potential in pharmaceutical applications, and in the past, they were also used as taxonomic markers alongside the difficult and homoplasy-prone sponge morphology for species delineation (chemotaxonomy). The understanding of phylogenetic distribution and distinctiveness of metabolites to sponge lineages is pivotal to reveal pathways and evolution of compound production in sponges. This benefits the discovery rate and yield of bioprospecting for novel marine natural products by identifying lineages with high potential of being new sources of valuable sponge compounds. In this review, we summarize the current biochemical data on sponges and compare the metabolite distribution against a sponge phylogeny. We assess compound specificity to lineages, potential convergences, and suitability as diagnostic phylogenetic markers. Our study finds compound distribution corroborating current (molecular) phylogenetic hypotheses, which include yet unaccepted polyphyly of several demosponge orders and families. Likewise, several compounds and compound groups display a high degree of lineage specificity, which suggests homologous biosynthetic pathways among their taxa, which identifies yet unstudied species of this lineage as promising bioprospecting targets.


Assuntos
Poríferos/química , Animais , Organismos Aquáticos , Humanos , Filogenia , Fitoterapia , Poríferos/classificação
8.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445356

RESUMO

Ferritins comprise a conservative family of proteins found in all species and play an essential role in resistance to redox stress, immune response, and cell differentiation. Sponges (Porifera) are the oldest Metazoa that show unique plasticity and regenerative potential. Here, we characterize the ferritins of two cold-water sponges using proteomics, spectral microscopy, and bioinformatic analysis. The recently duplicated conservative HdF1a/b and atypical HdF2 genes were found in the Halisarca dujardini genome. Multiple related transcripts of HpF1 were identified in the Halichondria panicea transcriptome. Expression of HdF1a/b was much higher than that of HdF2 in all annual seasons and regulated differently during the sponge dissociation/reaggregation. The presence of the MRE and HRE motifs in the HdF1 and HdF2 promotor regions and the IRE motif in mRNAs of HdF1 and HpF indicates that sponge ferritins expression depends on the cellular iron and oxygen levels. The gel electrophoresis combined with specific staining and mass spectrometry confirmed the presence of ferric ions and ferritins in multi-subunit complexes. The 3D modeling predicts the iron-binding capacity of HdF1 and HpF1 at the ferroxidase center and the absence of iron-binding in atypical HdF2. Interestingly, atypical ferritins lacking iron-binding capacity were found in genomes of many invertebrate species. Their function deserves further research.


Assuntos
Ferritinas/genética , Poríferos/genética , Animais , Sequência Conservada , Ferritinas/química , Ferritinas/metabolismo , Ferro/metabolismo , Redes e Vias Metabólicas/genética , Modelos Moleculares , Filogenia , Poríferos/classificação , Poríferos/metabolismo , Domínios Proteicos/genética , Análise de Sequência de DNA , Transcriptoma/fisiologia
10.
Zootaxa ; 4990(3): 596-600, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34186738

RESUMO

Four species of Phlyctaenopora Topsent, 1904 (Demospongiae Sollas, Poecilosclerida Topsent, Mycalidae Lundbeck) are recognised today (Van Soest et al. 2021a) (Table 1): two Atlantic Ocean species in subgenus Phlyctaenopora [type species P. (P.) bitorquis Topsent, 1904, from the Azores; P. (P.) halichondrioides van Soest Stentoft, 1988, from Barbados]; and two Southern Hemisphere species in subgenus Barbozia Dendy, 1922: P. (Barbozia) primitiva Dendy, 1922, from the Seychelles, and P. (B.) bocagei Lévi Lévi, 1983, from New Caledonia. Here we describe a new species of Phlyctaenopora from Wanganella North in International Waters on the West Norfolk Ridge, northwest of New Zealand. Phlyctaenopora (B.) spina sp. nov. provides a first record of the genus in the South Pacific, providing further confirmation of the integrity of the subgenus Barbozia.


Assuntos
Poríferos/classificação , Animais , Nova Zelândia , Oceano Pacífico
12.
Zootaxa ; 4970(2): 353371, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34186890

RESUMO

Sponges (phylum Porifera) are common inhabitants of kelp forest ecosystems in California, but their diversity and ecological importance are poorly characterized in this biome. Here I use freshly collected samples to describe the diversity of the order Scopalinida in California. Though previously unknown in the region, four new species are described here: Scopalina nausicae sp. nov., S. kuyamu sp. nov., S. goletensis sp. nov., and S. jali sp. nov.. These discoveries illustrate the considerable uncharacterized sponge diversity remaining in California kelp forests, and the utility of SCUBA-based collection to improve our understanding of this diversity.


Assuntos
Poríferos/classificação , Animais , California , Ecossistema , Kelp , Oceano Pacífico
13.
Zootaxa ; 4981(1): 4769, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34186957

RESUMO

The sponge genus Corticium has important evolutionary significance and great pharmacological potential, but its diversity remains poorly known. In this contribution we redescribe two poorly-known Indian and Pacific oceans species, viz., Corticium simplex and C. bargibanti, and describe three new species of Corticium from Western Australia. We observed for the first time the presence of rare calthrops in C. simplex, which has a wide distribution and may be a species complex. The three new species are mainly characterized by their spiculation: Corticium furcatum sp. nov. has large calthrops and exclusive candelabra with bifurcated rays in the apical actine; C. monolophum sp. nov. has large monolophose calthrops, smooth calthrops and candelabra; and C. verticillatum sp. nov. has acanthocalthrops with verticillated spines, which are exclusive to this species within the genus. The diversity of Corticium is raised to 11 species worldwide, but it still remains highly underestimated. A key to all valid species is here provided.


Assuntos
Poríferos/classificação , Animais , Oceano Pacífico , Filogenia , Austrália Ocidental
14.
Zootaxa ; 4979(1): 3856, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34187015

RESUMO

The peer-reviewed journal Zootaxa has accelerated the rate of sponge (Porifera) species discoveries in 289 peer-reviewed papers published between 2002 up until the end of 2020, describing 725 new species, six new subspecies, 27 new genera, four new subgenera, and 123 new species and genus names needed to resolve existing homonyms. Zootaxa has been the most prolific of all taxonomic journals in its contributions to describing new taxa of Porifera in modern times. This present article analyses these taxonomic contributions over the past 20 years of Zootaxa, including their trends and highlights pertaining to sponge publications.


Assuntos
Poríferos/classificação , Animais , Publicações Periódicas como Assunto
15.
Zootaxa ; 4912(1): zootaxa.4912.1.1, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33756595

RESUMO

The species of the cosmopolitan sponge genus Mycale occurring in the tropical Indo-West Pacific region and adjacent subtropical waters are reviewed taxonomically. Specimens incorporated in the collections of the Naturalis Biodiversity Center form the basis of this comprehensive study, supplemented by (type) specimens borrowed from or examined in other institutions. Specimens available numbered 351, belonging to 44 species, including 14 species new to science, Mycale (Aegogropila) prognatha sp.nov., Mycale (Carmia) amiri sp.nov., Mycale (Carmia) fungiaphila sp.nov., Mycale (Carmia) monomicrosclera sp.nov., Mycale (Carmia) tenuichela sp.nov., Mycale (Carmia) tubiporicola sp.nov., Mycale (Carmia) tydemani sp.nov., Mycale (Mycale) asigmata sp.nov., Mycale (Mycale) grandoides sp.nov., Mycale (Mycale) sundaminorensis sp.nov., Mycale (Naviculina) mascarenensis sp.nov., Mycale (Paresperella) sceptroides sp.nov., Mycale (Paresperella) seychellensis sp.nov., Mycale (Zygomycale) sibogae sp.nov. Three species, indicated by the designation 'aff.', were not definitely assigned to known or new species due to uncertainty of their identity. The genus Kerasemna, previously considered a junior synonym of Mycale, was revived as an additional subgenus Mycale (Kerasemna). One species, previously assigned to the genus Desmacella as D. lampra De Laubenfels is here reassigned to Mycale, subgenus at present undecided. Additionally, species previously reported from the region but not represented in our collections are briefly characterized and discussed. We propose new names Mycale (Mycale) mauricei nom.nov. for Mycale macrochela Burton (junior primary homonym of Mycale fistulata var. macrochela Hentschel) and Mycale (Mycale) bouryesnaultae nom.nov. for Mycale (Mycale) fibrosa Boury-Esnault Van Beveren (junior primary homonym of Mycale (Aegogropila) adhaerens subsp. fibrosa Koltun). Keys to the species of each subgenus occurring in the region are provided. The opportunity of having studied this comprehensive set of species and specimens from the tropical Indo-West Pacific is taken to review and discuss the morphological and biogeographical data gathered so far on the genus Mycale. The genus currently comprises approximately 255 accepted species, with highest diversity focused in tropical Atlantic and Indo-West Pacific regions as well as in warm-temperate Mediterranean-Atlantic regions.


Assuntos
Biodiversidade , Filogenia , Poríferos/classificação , Animais
16.
Nat Commun ; 12(1): 1783, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741994

RESUMO

Resolving the relationships between the major lineages in the animal tree of life is necessary to understand the origin and evolution of key animal traits. Sponges, characterized by their simple body plan, were traditionally considered the sister group of all other animal lineages, implying a gradual increase in animal complexity from unicellularity to complex multicellularity. However, the availability of genomic data has sparked tremendous controversy as some phylogenomic studies support comb jellies taking this position, requiring secondary loss or independent origins of complex traits. Here we show that incorporating site-heterogeneous mixture models and recoding into partitioned phylogenomics alleviates systematic errors that hamper commonly-applied phylogenetic models. Testing on real datasets, we show a great improvement in model-fit that attenuates branching artefacts induced by systematic error. We reanalyse key datasets and show that partitioned phylogenomics does not support comb jellies as sister to other animals at either the supermatrix or partition-specific level.


Assuntos
Ctenóforos/genética , Genoma/genética , Genômica/métodos , Filogenia , Poríferos/genética , Animais , Evolução Biológica , Ctenóforos/classificação , Modelos Genéticos , Poríferos/classificação , Especificidade da Espécie
17.
Curr Biol ; 31(4): R202-R204, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33621510

RESUMO

Animal phylogeny has always been controversial, but a new study brings some much-needed order for two infamous wandering groups, the ctenophores and the Xenacoelomorphs. The study introduces an innovative approach to dissect systematic errors in the underlying methodology of molecular phylogenies.


Assuntos
Ctenóforos/classificação , Filogenia , Poríferos/classificação , Animais , Projetos de Pesquisa
18.
mSphere ; 6(1)2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536324

RESUMO

Climate change is expanding marine oxygen minimum zones (OMZs), while anthropogenic nutrient input depletes oxygen concentrations locally. The effects of deoxygenation on animals are generally detrimental; however, some sponges (Porifera) exhibit hypoxic and anoxic tolerance through currently unknown mechanisms. Sponges harbor highly specific microbiomes, which can include microbes with anaerobic capabilities. Sponge-microbe symbioses must also have persisted through multiple anoxic/hypoxic periods throughout Earth's history. Since sponges lack key components of the hypoxia-inducible factor (HIF) pathway responsible for hypoxic responses in other animals, it was hypothesized that sponge tolerance to deoxygenation may be facilitated by its microbiome. To test this hypothesis, we determined the microbial composition of sponge species tolerating seasonal anoxia and hypoxia in situ in a semienclosed marine lake, using 16S rRNA amplicon sequencing. We discovered a high degree of cryptic diversity among sponge species tolerating seasonal deoxygenation, including at least nine encrusting species of the orders Axinellida and Poecilosclerida. Despite significant changes in microbial community structure in the water, sponge microbiomes were species specific and remarkably stable under varied oxygen conditions, which was further explored for Eurypon spp. 2 and Hymeraphia stellifera However, some symbiont sharing occurred under anoxia. At least three symbiont combinations, all including large populations of Thaumarchaeota, corresponded with deoxygenation tolerance, and some combinations were shared between some distantly related hosts. We propose hypothetical host-symbiont interactions following deoxygenation that could confer deoxygenation tolerance.IMPORTANCE The oceans have an uncertain future due to anthropogenic stressors and an uncertain past that is becoming clearer with advances in biogeochemistry. Both past and future oceans were, or will be, deoxygenated in comparison to present conditions. Studying how sponges and their associated microbes tolerate deoxygenation provides insights into future marine ecosystems. Moreover, sponges form the earliest branch of the animal evolutionary tree, and they likely resemble some of the first animals. We determined the effects of variable environmental oxygen concentrations on the microbial communities of several demosponge species during seasonal anoxia in the field. Our results indicate that anoxic tolerance in some sponges may depend on their symbionts, but anoxic tolerance was not universal in sponges. Therefore, some sponge species could likely outcompete benthic organisms like corals in future, reduced-oxygen ecosystems. Our results support the molecular evidence that sponges and other animals have a Neoproterozoic origin and that animal evolution was not limited by low-oxygen conditions.


Assuntos
Bactérias/genética , Lagos/microbiologia , Microbiota/genética , Microbiota/fisiologia , Poríferos/microbiologia , Estações do Ano , Anaerobiose , Animais , Organismos Aquáticos , Bactérias/classificação , Bactérias/isolamento & purificação , Fenômenos Fisiológicos Bacterianos , Mudança Climática , Variação Genética , Interações entre Hospedeiro e Microrganismos , Irlanda , Filogenia , Poríferos/classificação , Poríferos/genética , Poríferos/fisiologia
19.
Mar Drugs ; 19(1)2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33435402

RESUMO

Marine sponges are exceptionally prolific sources of natural products for the discovery and development of new drugs. Until now, sponges have contributed around 30% of all natural metabolites isolated from the marine environment. Family Latrunculiidae Topsent, 1922 (class Demospongiae Sollas, 1885, order Poecilosclerida Topsent, 1928) is a small sponge family comprising seven genera. Latrunculid sponges are recognized as the major reservoirs of diverse types of pyrroloiminoquinone-type alkaloids, with a myriad of biological activities, in particular, cytotoxicity, fuelling their exploration for anticancer drug discovery. Almost 100 pyrroloiminoquinone alkaloids and their structurally related compounds have been reported from the family Latrunculiidae. The systematics of latrunculid sponges has had a complex history, however it is now well understood. The pyrroloiminoquinone alkaloids have provided important chemotaxonomic characters for this sponge family. Latrunculid sponges have been reported to contain other types of metabolites, such as peptides (callipeltins), norditerpenes and norsesterpenes (trunculins) and macrolides (latrunculins), however, the sponges containing latrunculins and trunculins have been transferred to other sponge families. This review highlights a comprehensive literature survey spanning from the first chemical investigation of a New Zealand Latrunculia sp. in 1986 until August 2020, focusing on the chemical diversity and biological activities of secondary metabolites reported from the family Latrunculiidae. The biosynthetic (microbial) origin and the taxonomic significance of pyrroloiminoquinone related alkaloids are also discussed.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Poríferos/química , Poríferos/classificação , Animais , Descoberta de Drogas , Humanos , Estrutura Molecular , Poríferos/metabolismo
20.
Biomolecules ; 10(10)2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33027969

RESUMO

Chloroethylagelastatin A (CEAA) is an analogue of agelastatin A (AA), a natural alkaloid derived from a marine sponge. It is under development for therapeutic use against brain tumors as it has excellent central nervous system (CNS) penetration and pre-clinical therapeutic activity against brain tumors. Recently, AA was shown to inhibit protein synthesis by binding to the ribosomal A-site. In this study, we developed a novel virtual screening platform to perform a comprehensive screening of various AA analogues showing that AA analogues with proven therapeutic activity including CEAA have significant ribosomal binding capacity whereas therapeutically inactive analogues show poor ribosomal binding and revealing structural fingerprint features essential for drug-ribosome interactions. In particular, CEAA was found to have greater ribosomal binding capacity than AA. Biological tests showed that CEAA binds the ribosome and contributes to protein synthesis inhibition. Our findings suggest that CEAA may possess ribosomal inhibitor activity and that our virtual screening platform may be a useful tool in discovery and development of novel ribosomal inhibitors.


Assuntos
Alcaloides , Antineoplásicos , Neoplasias Encefálicas , Poríferos/classificação , Ribossomos , Alcaloides/química , Alcaloides/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Proteínas de Neoplasias/biossíntese , Biossíntese de Proteínas/efeitos dos fármacos , Ribossomos/química , Ribossomos/metabolismo
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