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1.
J Med Microbiol ; 69(8): 1040-1048, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32692643

RESUMO

Given the increased reporting of multi-resistant bacteria and the shortage of newly approved medicines, researchers have been looking towards extreme and unusual environments as a new source of antibiotics. Streptomyces currently provides many of the world's clinical antibiotics, so it comes as no surprise that these bacteria have recently been isolated from traditional medicine. Given the wide array of traditional medicines, it is hoped that these discoveries can provide the much sought after core structure diversity that will be required of a new generation of antibiotics. This review discusses the contribution of Streptomyces to antibiotics and the potential of newly discovered species in traditional medicine. We also explore how knowledge of traditional medicines can aid current initiatives in sourcing new and chemically diverse antibiotics.


Assuntos
Antibacterianos/isolamento & purificação , Descoberta de Drogas/tendências , Microbiologia do Solo , Streptomyces/metabolismo , Animais , Antibacterianos/biossíntese , Cavernas/química , Invertebrados/química , Medicina Tradicional , Peptídeo Sintases/metabolismo , Plantas Medicinais/química , Policetídeo Sintases/metabolismo , Poríferos/química , Streptomyces/química , Streptomyces/enzimologia
2.
Int J Nanomedicine ; 15: 3377-3389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494136

RESUMO

Background: Hepatitis C virus (HCV) infection is a major cause of hepatic diseases all over the world. This necessitates the need to discover novel anti-HCV drugs to overcome emerging drug resistance and liver complications. Purpose: Total extract and petroleum ether fraction of the marine sponge (Amphimedon spp.) were used for silver nanoparticle (SNP) synthesis to explore their HCV NS3 helicase- and protease-inhibitory potential. Methods: Characterization of the prepared SNPs was carried out with ultraviolet-visible spectroscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy. The metabolomic profile of different Amphimedon fractions was assessed using liquid chromatography coupled with high-resolution mass spectrometry. Fourteen known compounds were isolated and their HCV helicase and protease activities assessed using in silico modeling of their interaction with both HCV protease and helicase enzymes to reveal their anti-HCV mechanism of action. In vitro anti-HCV activity against HCV NS3 helicase and protease was then conducted to validate the computation results and compared to that of the SNPs. Results: Transmission electron-microscopy analysis of NPs prepared from Amphimedon total extract and petroleum ether revealed particle sizes of 8.22-14.30 nm and 8.22-9.97 nm, and absorption bands at λmax of 450 and 415 nm, respectively. Metabolomic profiling revealed the richness of Amphimedon spp. with different phytochemical classes. Bioassay-guided isolation resulted in the isolation of 14 known compounds with anti-HCV activity, initially revealed by docking studies. In vitro anti-HCV NS3 helicase and protease assays of both isolated compounds and NPs further confirmed the computational results. Conclusion: Our findings indicate that Amphimedon, total extract, petroleum ether fraction, and derived NPs are promising biosources for providing anti-HCV drug candidates, with nakinadine B and 3,4-dihydro-6-hydroxymanzamine A the most potent anti-HCV agents, possessing good oral bioavailability and penetration power.


Assuntos
Simulação por Computador , DNA Helicases/antagonistas & inibidores , Química Verde , Metabolômica , Nanopartículas Metálicas/química , Poríferos/química , Prata/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Alcanos/química , Animais , Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Oceano Índico , Nanopartículas Metálicas/ultraestrutura , Simulação de Acoplamento Molecular , Peptídeo Hidrolases/metabolismo , Inibidores de Proteases/farmacologia , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Mar Drugs ; 18(2)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054048

RESUMO

Latrunculia sponges represent a rich source of discorhabdin-type pyrroloiminoquinone alkaloids, a few of which comprise a dimeric structure. The anticancer-activity-guided isolation of the n-hexane subextract of the Antarctic deep-sea sponge Latrunculia biformis yielded the known compound (-)-(1R,2R,6R,8S,6'S)-discorhabdin B dimer (1) and two new derivatives, (-)-(1S,2R,6R,8S,6'S)-discorhabdin B dimer (2) and (-)-(1R,2R,6R,8S,6'S)-16',17'-dehydrodiscorhabdin B dimer (3). The chemical structures of compounds 1-3 were elucidated by means of HR-ESIMS, NMR, [], ECD spectroscopy, and a comparison with the previously reported discorhabdin analogs. Compounds 1 and 2 showed significant in vitro anticancer activity against the human colon cancer cell line (HCT-116), with IC50 values of 0.16 and 2.01 µM, respectively. Compared to monomeric discorhabdins, dimeric discorhabdins are very rare in Nature. This study adds two new discorhabdin dimers (2 and 3) to this small pyrroloiminoquinone subfamily. This is also the first report of compound 1 as a natural product and the first assessment of its in vitro anticancer activity.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Poríferos/química , Quinolonas/química , Quinolonas/farmacologia , Tiazepinas/química , Tiazepinas/farmacologia , Animais , Produtos Biológicos , Neoplasias do Colo , Doxorrubicina/farmacologia , Células HCT116 , Humanos , Concentração Inibidora 50 , Queratinócitos , Estrutura Molecular
5.
Nat Commun ; 11(1): 373, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953388

RESUMO

The layered architecture of stiff biological materials often endows them with surprisingly high fracture toughness in spite of their brittle ceramic constituents. Understanding the link between organic-inorganic layered architectures and toughness could help to identify new ways to improve the toughness of biomimetic engineering composites. We study the cylindrically layered architecture found in the spicules of the marine sponge Euplectella aspergillum. We cut micrometer-size notches in the spicules and measure their initiation toughness and average crack growth resistance using flexural tests. We find that while the spicule's architecture provides toughness enhancements, these enhancements are relatively small compared to prototypically tough biological materials, like nacre. We investigate these modest toughness enhancements using computational fracture mechanics simulations.


Assuntos
Materiais Biocompatíveis , Materiais Biomiméticos/química , Resinas Compostas/química , Resistência à Flexão , Poríferos/química , Animais , Fenômenos Biomecânicos , Cerâmica/química , Dureza , Teste de Materiais , Modelos Teóricos , Nácar/química , Estresse Mecânico , Propriedades de Superfície
6.
Mar Drugs ; 18(2)2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31991544

RESUMO

In the current study, an NMR spectroscopic pattern-based procedure for probing scalarane derivatives was performed and four new 24-homoscalaranes, lendenfeldaranes A-D (1- 4), along with three known compounds, 12α-acetoxy-22-hydroxy-24-methyl-24-oxoscalar-16-en- 25-al (5), felixin F (6), and 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (7) were isolated from the sponge Lendenfeldia sp. The structures of scalaranes 1-7 were elucidated on the basis of spectroscopic analysis. Scalaranes 1-7 were further evaluated for their cytotoxicity toward a series of human cancer cell lines and the results suggested that 5 and 7 dominated in the anti- proliferative activity of the extract. The 18-aldehyde functionality was found to play a key role in their activity.


Assuntos
Proliferação de Células/efeitos dos fármacos , Poríferos/química , Sesterterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesterterpenos/química , Sesterterpenos/isolamento & purificação
7.
Nat Prod Res ; 34(8): 1113-1117, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30663370

RESUMO

A new thiodiketopiperzaine, tedanizaine A (1), together with six known ones, were isolated from the marine sponge Tedania sp. Their structures were determined by spectroscopic analyses. The absolute configuration of 1 was established by ECD calculation. Compound 1 was the second example of thiodiketopiperazine bearing a thiazolidine unit. Cytotoxic activities of 1 were also evaluated.


Assuntos
Citotoxinas/isolamento & purificação , Dicetopiperazinas/isolamento & purificação , Poríferos/química , Tiazóis/isolamento & purificação , Animais , Linhagem Celular , Citotoxinas/química , Citotoxinas/farmacologia , Dicetopiperazinas/química , Dicetopiperazinas/farmacologia , Humanos , Conformação Molecular , Estrutura Molecular , Análise Espectral , Tiazóis/química , Tiazóis/farmacologia
8.
Nat Prod Res ; 34(5): 710-713, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30445822

RESUMO

The correlation between the allocation of trisoxazole macrolides in the capitums, appendages, and bases of the sponge Penares cf. nux and the surface-attached bacteria on the corresponding parts was examined. The kabiramide contents were highest in the capitums, followed by the appendages and bases. Conversely, direct counts of cultivable surface-attached bacteria showed that the bacteria aggregate more densely on the surfaces of the bases. This suggested the repelling effects of the kabiramides against the fouling bacteria, particularly on the capitums and appendages. Twenty-two bacterial strains were isolated and identified to 15 species; however, none has shown the potentials as a producer of any secondary metabolites in the sponge P. nux.


Assuntos
Antibacterianos/metabolismo , Macrolídeos/farmacologia , Poríferos/metabolismo , Animais , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Aderência Bacteriana/fisiologia , Macrolídeos/metabolismo , Oxazóis/metabolismo , Oxazóis/farmacologia , Poríferos/química
9.
Nat Prod Res ; 34(6): 790-796, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30445862

RESUMO

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].


Assuntos
Antineoplásicos/isolamento & purificação , Citotoxinas/isolamento & purificação , Poríferos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacologia , Dicetopiperazinas/isolamento & purificação , Diterpenos/isolamento & purificação , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Esteróis/isolamento & purificação , Terpenos/isolamento & purificação
10.
Nat Prod Res ; 34(8): 1053-1060, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30584768

RESUMO

Two new marine natural compounds, 3ß-acetoxy-15-hydroxyspongia-12-en (1) and 3-methylspongia-3,12-dien-16-one (2), were isolated from the marine sponge Acanthodendrilla sp., collected in Pulau-Pulau. Compounds 1 and 2 represent new chemical entities of the known spongian diterpene family. Compound 1 is a new 3-acetoxyspongia and compound 2 presents an unreported rearranged 3-methylspongia-3-en. Their structures, including relative configurations, were fully elucidated based on 1D and 2D NMR analyses, as well as HRESTOFMS experiments. No significant bioactivities were found for these compounds. This work reports two new chemical structures, compounds 1 and 2, together with the first isolation of spongian diterpenes from Acanthodendrilla genus.


Assuntos
Diterpenos/isolamento & purificação , Poríferos/química , Animais , Diterpenos/química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular
11.
Mar Drugs ; 17(12)2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31771152

RESUMO

Here, we report the therapeutic potential of a natural quinazoline derivative (2-chloro-6-phenyl-8H-quinazolino[4,3-b]quinazolin-8-one) isolated from marine sponge Hyrtios erectus against human breast cancer. The cytotoxicity of the compound was investigated on a human breast carcinoma cell line (MCF-7). Antiproliferative activity of the compound was estimated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MTT assay showed significant inhibition of MCF-7 cells viability with the IC50 value of 13.04 ± 1.03 µg/mL after 48 h. The compound induced down-regulation of anti-apoptotic Bcl-2 protein and increase in the pro-apoptotic Bax/Bcl-2 ratio in MCF-7 cells. The compound activated the expression of Caspases-9 and stimulated downstream signal transducer Caspase-7. In addition, Caspase-8 showed remarkable up-regulation in MCF-7 cells treated with the compound. Moreover, the compound was found to promote oxidative stress in MCF-7 cells that led to cell death. In conclusion, the compound could induce apoptosis of breast carcinoma cells via a mechanism that involves ROS production and either extrinsic or intrinsic apoptosis pathways. The systemic toxic potential of the compound was evaluated in an in vivo mouse model, and it was found non-toxic to the major organs.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias da Mama/tratamento farmacológico , Poríferos/química , Quinazolinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Concentração Inibidora 50 , Células MCF-7 , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Quinazolinas/isolamento & purificação , Quinazolinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Testes de Toxicidade Aguda
12.
Mar Drugs ; 17(11)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717394

RESUMO

The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn's disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal (1) along with four known compounds from the sponge genus Phyllospongia. The anti-inflammatory properties of deacetylphylloketal (1) and phyllohemiketal A (2) were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds 1 or 2 significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1ß and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that 1 and 2 markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus Phyllospongia and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Poríferos/química , Sesterterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Células CACO-2 , Linhagem Celular , Técnicas de Cocultura , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Sesterterpenos/isolamento & purificação
13.
Mar Drugs ; 17(11)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671549

RESUMO

Caribbean sponges of the genus Smenospongia are a prolific source of chlorinated secondary metabolites. The use of molecular networking as a powerful dereplication tool revealed in the metabolome of S. aurea two new members of the smenamide family, namely smenamide F (1) and G (2). The structure of smenamide F (1) and G (2) was determined by spectroscopic analysis (NMR, MS, ECD). The relative and the absolute configuration at C-13, C-15, and C-16 was determined on the basis of the conformational rigidity of a 1,3-disubstituted alkyl chain system (i.e., the C-12/C-18 segment of compound (1). Smenamide F (1) and G (2) were shown to exert a selective moderate antiproliferative activity against cancer cell lines MCF-7 and MDA-MB-231, while being inactive against MG-63.


Assuntos
Produtos Biológicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Poríferos/química , Animais , Antineoplásicos/farmacologia , Região do Caribe , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fibroblastos , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Metaboloma , Estrutura Molecular , Poríferos/metabolismo
14.
Molecules ; 24(21)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671793

RESUMO

As part of an ongoing program to identify new bioactive compounds from Irish marine bioresources, we selected the subtidal sponge Spongosorites calcicola for chemical study, as fractions of this species displayed interesting cytotoxic bioactivities and chemical profiles. The first chemical investigation of this marine species led to the discovery of two new bisindole alkaloids of the topsentin family, together with six other known indole alkaloids. Missing the usual central core featured by the representatives of these marine natural products, the new metabolites may represent key biosynthetic intermediates for other known bisindoles. These compounds were found to exhibit weak cytotoxic activity against HeLa tumour cells, suggesting a specificity towards previously screened carcinoma and leukaemia cells.


Assuntos
Halogenação , Alcaloides Indólicos/farmacologia , Poríferos/química , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Teoria da Densidade Funcional , Células HeLa , Humanos , Alcaloides Indólicos/síntese química , Alcaloides Indólicos/química , Espectroscopia de Prótons por Ressonância Magnética
15.
Int J Mol Sci ; 20(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618840

RESUMO

Marine sponges remain representative of a unique source of renewable biological materials. The demosponges of the family Ianthellidae possess chitin-based skeletons with high biomimetic potential. These three-dimensional (3D) constructs can potentially be used in tissue engineering and regenerative medicine. In this study, we focus our attention, for the first time, on the marine sponge Ianthella labyrinthus Bergquist & Kelly-Borges, 1995 (Demospongiae: Verongida: Ianthellidae) as a novel potential source of naturally prestructured bandage-like 3D scaffolds which can be isolated simultaneously with biologically active bromotyrosines. Specifically, translucent and elastic flat chitinous scaffolds have been obtained after bromotyrosine extraction and chemical treatments of the sponge skeleton with alternate alkaline and acidic solutions. For the first time, cardiomyocytes differentiated from human induced pluripotent stem cells (iPSC-CMs) have been used to test the suitability of I. labyrinthus chitinous skeleton as ready-to-use scaffold for their cell culture. Results reveal a comparable attachment and growth on isolated chitin-skeleton, compared to scaffolds coated with extracellular matrix mimetic Geltrex®. Thus, the natural, unmodified I. labyrinthus cleaned sponge skeleton can be used to culture iPSC-CMs and 3D tissue engineering. In addition, I. labyrinthus chitin-based scaffolds demonstrate strong and efficient capability to absorb blood deep into the microtubes due to their excellent capillary effect. These findings are suggestive of the future development of new sponge chitin-based absorbable hemostats as alternatives to already well recognized cellulose-based fabrics.


Assuntos
Organismos Aquáticos/química , Materiais Biocompatíveis/química , Produtos Biológicos/química , Poríferos/química , Animais , Curativos Biológicos , Quitina/química , Humanos , Impressão Tridimensional , Engenharia Tecidual , Tecidos Suporte/química
16.
Mar Drugs ; 17(11)2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31652835

RESUMO

There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus-a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 ± 0.74 µM) and L4 motility (IC50 = 39.4 ± 4.83 µM), although it had a relatively low potency at inhibiting of xL3 motility (IC50 ≥ 100 µM). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts.


Assuntos
Alcaloides/farmacologia , Anti-Helmínticos/farmacologia , Haemonchus/efeitos dos fármacos , Alcaloides/química , Animais , Anti-Helmínticos/química , Austrália , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Poríferos/química , Ratos
17.
Mar Drugs ; 17(10)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658704

RESUMO

Naturally occurring three-dimensional (3D) biopolymer-based matrices that can be used in different biomedical applications are sustainable alternatives to various artificial 3D materials. For this purpose, chitin-based structures from marine sponges are very promising substitutes. Marine sponges from the order Verongiida (class Demospongiae) are typical examples of demosponges with well-developed chitinous skeletons. In particular, species belonging to the family Ianthellidae possess chitinous, flat, fan-like fibrous skeletons with a unique, microporous 3D architecture that makes them particularly interesting for applications. In this work, we focus our attention on the demosponge Ianthella flabelliformis (Linnaeus, 1759) for simultaneous extraction of both naturally occurring ("ready-to-use") chitin scaffolds, and biologically active bromotyrosines which are recognized as potential antibiotic, antitumor, and marine antifouling substances. We show that selected bromotyrosines are located within pigmental cells which, however, are localized within chitinous skeletal fibers of I. flabelliformis. A two-step reaction provides two products: treatment with methanol extracts the bromotyrosine compounds bastadin 25 and araplysillin-I N20 sulfamate, and a subsequent treatment with acetic acid and sodium hydroxide exposes the 3D chitinous scaffold. This scaffold is a mesh-like structure, which retains its capillary network, and its use as a potential drug delivery biomaterial was examined for the first time. The results demonstrate that sponge-derived chitin scaffolds, impregnated with decamethoxine, effectively inhibit growth of the human pathogen Staphylococcus aureus in an agar diffusion assay.


Assuntos
Organismos Aquáticos/química , Quitina/química , Portadores de Fármacos/química , Poríferos/química , Tirosina/análogos & derivados , Animais , Antibacterianos/administração & dosagem , Quitina/isolamento & purificação , Citoesqueleto/química , Compostos de Decametônio/administração & dosagem , Portadores de Fármacos/isolamento & purificação , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/isolamento & purificação , Isoxazóis/química , Isoxazóis/isolamento & purificação , Testes de Sensibilidade Microbiana , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Poríferos/citologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Tirosina/química , Tirosina/isolamento & purificação
18.
Mar Drugs ; 17(10)2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31569349

RESUMO

Pregnane X Receptor (PXR) is a ligand-activated transcription factor which binds many structurally different molecules. The receptor is able to regulate the expression of a wide array of genes and is involved in cancer and different key physiological processes such as the metabolism of drugs/xenobiotics and endogenous compounds including lipids and carbohydrates, and inflammation. Algae, sponges, sea squirts, and other marine organisms are some of the species from which structurally new molecules have been isolated that have been subsequently identified in recent decades as ligands for PXR. The therapeutic potential of these natural compounds is promising in different areas and has recently resulted in the registration of trabectedin by the FDA as a novel antineoplastic drug. Apart from being potentially novel drugs, these compounds can also serve as models for the development of new molecules with improved activity. The aim of this review is to succinctly summarize the currently known natural molecules isolated from marine organisms with a proven ability to interact with PXR.


Assuntos
Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Desenvolvimento de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Receptor de Pregnano X/metabolismo , Animais , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Humanos , Ligantes , Estrutura Molecular , Poríferos/química , Urocordados/química
19.
Molecules ; 24(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540496

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10Z)-debromohymenialdisine (1) isolated from marine sponge Stylissa species using an intestinal in vitro model with a transwell co-culture system. The treatment with 1 attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1ß, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1-5 µM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that 1 markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of 1 as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.


Assuntos
Organismos Aquáticos/química , Azepinas/farmacologia , Colite Ulcerativa , Doença de Crohn , Intestinos/patologia , Poríferos/química , Pirróis/farmacologia , Animais , Azepinas/química , Células CACO-2 , Técnicas de Cocultura , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Dinoprostona/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pirróis/química , Células THP-1
20.
Biosci Biotechnol Biochem ; 83(12): 2198-2201, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31429643

RESUMO

The first synthesis of phorbasin H, a diterpene carboxylic acid isolated from the sponge Phorbas gukulensis, was achieved using 1,4-trans-cyclohexanedimethanol and (S)-citronellal as starting materials. The data collected in this synthesis indicated the absolute configuration of the naturally occurring phorbasin H to be S.


Assuntos
Ácidos Carboxílicos/química , Diterpenos/química , Diterpenos/síntese química , Poríferos/química , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Diterpenos/isolamento & purificação , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray
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