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1.
Molecules ; 26(4)2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33669688

RESUMEN

Marine sponges are one of the prolific producers of bioactive natural products with therapeutic potential. As an important subgenus of Haliclona, Reniera sponges are mainly distributed in the Mediterranean Sea and Atlantic area, and had been chemically investigated for over four decades. By an extensive literature search, this review first makes a comprehensive summary of all natural products from Reniera sponges and their endozoic microbes, as well as biological properties. Perspectives on strengthening the chemical study of Reniera sponges for new drug-lead discovery are provided in this work.


Asunto(s)
Organismos Acuáticos/química , Productos Biológicos/análisis , Poríferos/química , Animales , Productos Biológicos/química , Modelos Moleculares
2.
Molecules ; 26(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525521

RESUMEN

In continuation of our studies on a Vietnamese collection of a Stelletta sp., sponge we have isolated two new isomalabaricane triterpenoids, stellettins Q and R (1 and 2), and four new isomalabaricane-derived nor-terpenoids, stellettins S-V 3-6, along with previously known globostelletin N. Among them, compound 3 contains an acetylenic fragment, unprecedented in the isomalabaricane family and extremely rare in other marine sponge terpenoids. The structures and absolute configurations of all new compounds were established by extensive NMR, MS, and ECD analyses together with quantum-chemical modeling. Additionally, according to obtained new data we report the correction in stereochemistry of two asymmetric centers in the structures of two known isomalabaricanes, 15R,23S for globostelletin M and 15S,23R for globostelletin N.


Asunto(s)
Poríferos/química , Poríferos/metabolismo , Terpenos/química , Triterpenos/química , Alquinos/química , Animales
3.
J Med Chem ; 64(2): 1197-1219, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33417773

RESUMEN

Significant inhibition of Aurora B was achieved by the synthesis of simplified fragments of benzosceptrins and oroidin belonging to the marine pyrrole-2-aminoimidazoles metabolites isolated from sponges. Evaluation of kinase inhibition enabled the discovery of a synthetically accessible rigid acetylenic structural analogue EL-228 (1), whose structure could be optimized into the potent CJ2-150 (37). Here we present the synthesis of new inhibitors of Aurora B kinase, which is an important target for cancer therapy through mitosis regulation. The biologically oriented synthesis yielded several nanomolar inhibitors. The optimized compound CJ2-150 (37) showed a non-ATP competitive allosteric mode of action in a mixed-type inhibition for Aurora B kinase. Molecular docking identified a probable binding mode in the allosteric site "F" and highlighted the key interactions with the protein. We describe the improvement of the inhibitory potency and specificity of the novel scaffold as well as the characterization of the mechanism of action.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Aurora Quinasa B/antagonistas & inhibidores , Poríferos/química , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Adenosina Trifosfato/metabolismo , Regulación Alostérica , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Mitosis/efectos de los fármacos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad
4.
Mar Drugs ; 18(12)2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33348536

RESUMEN

The discovery of novel natural products (NPs) that will serve as lead structures has to be an ongoing effort to fill the respective development pipelines. However, identification of NPs, which possess a potential for application in e.g., the pharma or agro sector, must be as cost effective and fast as possible. Furthermore, the amount of sample available for initial testing is usually very limited, not least because of the fact that the impact on the environment, i.e., the sampled biosystem, should be kept minimal. Here, our pipeline SeaPEPR is described, in which a primary bioactivity screening of crude extracts is combined with the analysis of their metabolic fingerprint. This enabled prioritization of samples for subsequent microfractionation and dereplication of the active compounds early in the workflow. As a case study, 76 marine sponge-derived extracts were screened against a microbial screening panel. Thereunder, human pathogenic bacteria (Escherichia coli ATCC35218 and Staphylococcus aureus ATCC33592) and yeast (Candida albicans FH2173), as well as the phytopathogenic fungus Septoria tritici MUCL45407. Overall, nine extracts revealed activity against at least one test organism. Metabolic fingerprinting enabled assigning four active extracts into one metabolic group; therefore, one representative was selected for subsequent microfractionation. Dereplication of the active fractions showed a new dibrominated aplysinopsin and a hypothetical chromazonarol stereoisomer derivative. Furthermore, inhibitory activity against the common plant pest Septoria tritici was discovered for NPs of marine origin.


Asunto(s)
Productos Biológicos/química , Monitoreo del Ambiente/métodos , Extractos Vegetales/química , Animales , Automatización , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Tecnología Química Verde , Redes y Vías Metabólicas , Pruebas de Sensibilidad Microbiana , Poríferos/química
5.
Molecules ; 25(24)2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33371471

RESUMEN

The structural elucidation of primary and secondary peroxidation products, formed from complex lipids, is a challenge in lipid analysis. In the present study, rare minor oxidized cerebrosides, isolated from the extract of a far eastern deep-sea glass sponge, Aulosaccus sp., were analyzed as constituents of a multi-component RP-HPLC (high-performance liquid chromatography on reversed-phase column) fraction using NMR (nuclear magnetic resonance) spectroscopy, mass spectrometry, GC (gas chromatography), and chemical transformations (including hydrogenation or derivatization with dimethyl disulfide before hydrolysis). Eighteen previously unknown ß-D-glucopyranosyl-(1→1)-ceramides (1a-a//, 1b-b//, 2a-a//, 2b-b//, 3c-c//, 3d-d//) were shown to contain phytosphingosine-type backbones (2S,3S,4R,11Z)-2-aminoeicos-11-ene-1,3,4-triol (in 1), (2S,3S,4R,13Z)-2-aminoeicos-13-ene-1,3,4-triol (in 2), and (13S*,14R*)-2-amino-13,14-methylene-eicosane-1,3,4-triol (in 3). These backbones were N-acylated with straight-chain monoenoic (2R)-2-hydroxy acids that had allylic hydroperoxy/hydroxy/keto groups on C-17/ in the 15/E-23:1 chain (a-a//), C-16/ in the 17/E-23:1 (b-b//) and 14/E-22:1 (c-c//) chains, and C-15/ in the 16/E-22:1 chain (d-d//). Utilizing complementary instrumental and chemical methods allowed for the first detailed structural analysis of a complex mixture of glycosphingolipids, containing allylically oxygenated monoenoic acyl chains.


Asunto(s)
Amidas/química , Cerebrósidos/química , Ácidos Grasos/química , Oxígeno/química , Poríferos/química , Animales , Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Fase Inversa/métodos , Mezclas Complejas/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Glicoesfingolípidos/química , Lípidos/química
6.
J Med Microbiol ; 69(8): 1040-1048, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32692643

RESUMEN

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.


Asunto(s)
Antibacterianos/aislamiento & purificación , Descubrimiento de Drogas/tendencias , Microbiología del Suelo , Streptomyces/metabolismo , Animales , Antibacterianos/biosíntesis , Cuevas/química , Invertebrados/química , Medicina Tradicional , Péptido Sintasas/metabolismo , Plantas Medicinales/química , Sintasas Poliquetidas/metabolismo , Poríferos/química , Streptomyces/química , Streptomyces/enzimología
7.
Int J Nanomedicine ; 15: 3377-3389, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32494136

RESUMEN

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.


Asunto(s)
Simulación por Computador , ADN Helicasas/antagonistas & inhibidores , Tecnología Química Verde , Metabolómica , Nanopartículas del Metal/química , Poríferos/química , Plata/farmacología , Proteínas no Estructurales Virales/antagonistas & inhibidores , Alcanos/química , Animales , Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Océano Índico , Nanopartículas del Metal/ultraestructura , Simulación del Acoplamiento Molecular , Péptido Hidrolasas/metabolismo , Inhibidores de Proteasas/farmacología , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier
9.
Mar Drugs ; 18(2)2020 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-32054048

RESUMEN

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.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Poríferos/química , Quinolonas/química , Quinolonas/farmacología , Tiazepinas/química , Tiazepinas/farmacología , Animales , Productos Biológicos , Neoplasias del Colon , Doxorrubicina/farmacología , Células HCT116 , Humanos , Concentración 50 Inhibidora , Queratinocitos , Estructura Molecular
10.
Mar Drugs ; 18(2)2020 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-31991544

RESUMEN

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.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Poríferos/química , Sesterterpenos/farmacología , Animales , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Sesterterpenos/química , Sesterterpenos/aislamiento & purificación
11.
Nat Commun ; 11(1): 373, 2020 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-31953388

RESUMEN

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.


Asunto(s)
Materiales Biocompatibles , Materiales Biomiméticos/química , Resinas Compuestas/química , Resistencia Flexional , Poríferos/química , Animales , Fenómenos Biomecánicos , Cerámica/química , Dureza , Ensayo de Materiales , Modelos Teóricos , Nácar/química , Estrés Mecánico , Propiedades de Superficie
12.
Sci Rep ; 10(1): 570, 2020 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-31953459

RESUMEN

The aim of the present study was to investigate if patterns obtained from evaporating droplets of pharmaceutical preparations reveal the impact of succussion on such medicinal products. For this purpose, five pharmaceutical preparations (Echinacea 10-2, Baptisia 10-3, Baptisia 10-4, Luffa 10-4, and Spongia 10-6) were prepared according to the European Pharmacopoeia guidelines for the production of homeopathic remedies, in three variants each: with varying numbers of succussion strokes (i) 100, (ii) 10 (succussed samples), and (iii) zero (gently mixed, unsuccussed sample). System stability was studied by means of systematic positive control experiments. Patterns were evaluated by means of computerized image analysis regarding grey level distribution, texture, and fractality. For all investigated pharmaceutical preparations, significant differences were found between the succussed and gently mixed samples; whereas, all three samples (prepared with 100, 10 and zero succussion strokes) could be significantly differentiated for Luffa 10-4 and Spongia 10-6 for one image evaluation parameter each. Control experiments showed a reasonable stability of the experimental set-up.


Asunto(s)
Echinacea/química , Fabaceae/química , Luffa/química , Preparaciones Farmacéuticas/química , Poríferos/química , Animales , Entropía , Guías como Asunto , Materia Medica/química , Modelos Químicos , Fenómenos Físicos
13.
J Nat Med ; 74(2): 409-414, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31834571

RESUMEN

Three new polyacetylenic alcohols, siphonellanols A-C (1-3), together with two known polyacetylenic alcohols (4-5), were isolated from the CHCl3-soluble fraction of the methanolic extract of the marine sponge Siphonochalina siphonella, collected in Egypt. The structures of 1-3 were determined by spectroscopic analyses of their 1D-, 2D-NMR, and MS spectra and by comparisons with reported data. The cytotoxicity assay revealed that 1-3 exhibited moderate cytotoxic activities against a human cervical cancer cell line (HeLa), a human breast cancer cell line (MCF-7), and a human lung cancer cell line (A549) with IC50 values ranging from 25.9 to 69.2 µM.


Asunto(s)
Alcoholes/química , Polímero Poliacetilénico/química , Poríferos/química , Animales , Egipto , Humanos , Estructura Molecular
14.
Nat Prod Res ; 34(5): 710-713, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30445822

RESUMEN

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.


Asunto(s)
Antibacterianos/metabolismo , Macrólidos/farmacología , Poríferos/metabolismo , Animales , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Adhesión Bacteriana/fisiología , Macrólidos/metabolismo , Oxazoles/metabolismo , Oxazoles/farmacología , Poríferos/química
15.
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
16.
Nat Prod Res ; 34(8): 1053-1060, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30584768

RESUMEN

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.


Asunto(s)
Diterpenos/aislamiento & purificación , Poríferos/química , Animales , Diterpenos/química , Espectroscopía de Resonancia Magnética , Conformación Molecular , Estructura Molecular
17.
Nat Prod Res ; 34(8): 1113-1117, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30663370

RESUMEN

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.


Asunto(s)
Citotoxinas/aislamiento & purificación , Dicetopiperazinas/aislamiento & purificación , Poríferos/química , Tiazoles/aislamiento & purificación , Animales , Línea Celular , Citotoxinas/química , Citotoxinas/farmacología , Dicetopiperazinas/química , Dicetopiperazinas/farmacología , Humanos , Conformación Molecular , Estructura Molecular , Análisis Espectral , Tiazoles/química , Tiazoles/farmacología
18.
Nat Prod Rep ; 37(1): 55-79, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31046051

RESUMEN

Covering: up to the end of 2018Natural selection relentlessly drives the evolution of natural products, favoring those that enhance the survival of species. During this evolutionary journey, some natural products acquire heightened chemical reactivity towards environmental stimuli, most likely benefiting host species through more agile ecological responses, leading to superior survival outcomes (i.e., more potent and faster acting toxins and chemical defences, infection control, and intra/inter species chemical communication). Although knowledge of natural products informs our understanding of the living world, inspiring new medicines, agrochemicals and scientific tools, the study of chemically reactive natural products can be particularly informative, albeit quite challenging. For example, such natural products are often prone to facile transformations during handling, yielding new "un-natural" products commonly referred to as artifacts. These transformations can be induced by many stimuli, including modest changes in pH or temperature, or exposure to light or air (i.e., oxygen), or even common organic solvents or chromatography media. Sadly, in the race to explore and report on new natural products, knowledge of the relationship between chemically reactive natural products and their artifacts is not always recognised, documented or valued. This review seeks to recalibrate and encourage a greater awareness of the relationship between natural products and artifacts, by examining case studies in the field of marine natural products chemistry (i.e., natural products and associated artifacts from marine invertebrates and algae, and marine-derived microbes). While every effort has been made to provide a comprehensive coverage up to early 2019, any omissions are inadvertent not deliberate. Structured around the types of chemical transformations that can deliver artifacts, and the functional groups involved, the review concludes with observations on how to regulate, detect, rationalise and even exploit artifacts, going forward.


Asunto(s)
Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Productos Biológicos/metabolismo , Solventes/química , Acetona/química , Animales , Organismos Acuáticos , Ácidos Carboxílicos/química , Ácidos Carboxílicos/metabolismo , Concentración de Iones de Hidrógeno , Hidrólisis , Lactonas/química , Lactonas/metabolismo , Espectroscopía de Resonancia Magnética , Cloruro de Metileno/química , Oxidación-Reducción , Poríferos/química , Bases de Schiff
19.
J Nat Prod ; 82(12): 3450-3455, 2019 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-31833368

RESUMEN

Seven new nitrile-bearing polyacetylenes, named albanitriles A-G, were isolated from a marine sponge of the Mycale genus (Order: Poecilosclerida, Family: Mycalidae) collected near Albany, Western Australia. Structural elucidation was achieved using a combination of high-resolution mass spectrometry and ultraviolet/visible, infrared, and nuclear magnetic resonance spectroscopy. The compounds were found to possess moderate activity against Giardia duodenalis when compared to a metronidazole positive control.


Asunto(s)
Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/farmacología , Biología Marina , Nitrilos/farmacología , Polímero Poliacetilénico/farmacología , Poríferos/química , Animales , Bacillus subtilis/efectos de los fármacos , Candida albicans/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Escherichia coli/efectos de los fármacos , Giardia lamblia/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Nitrilos/química , Polímero Poliacetilénico/química , Análisis Espectral/métodos
20.
Mar Drugs ; 17(12)2019 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-31771152

RESUMEN

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.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Poríferos/química , Quinazolinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Ratones , Estrés Oxidativo/efectos de los fármacos , Quinazolinas/aislamiento & purificación , Quinazolinas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Pruebas de Toxicidad Aguda
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