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1.
Sci Rep ; 8(1): 6317, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29679028

RESUMO

Although radiation therapy is an effective treatment modality in many cancers, there is an urgent need to develop therapeutic drugs capable of overcoming radioresistance or minimizing normal tissue toxicity. A wide variety of marine-derived bioactive compounds have been screened for anti-cancer drug discovery, but little is known regarding radiation therapy applications. In this study, six different extracts of marine sponges collected from the Micronesian sea were screened for anti-cancer and radiosensitizing activity. Two extracts derived from Agelas sponges collected off the coast of Kosrae and Chuuk, the Federated States of Micronesia significantly decreased clonogenic survival of hepatocellular carcinoma (HCC) cells after exposure to ionizing radiation (IR). The Agelas extracts augmented IR-induced apoptosis and accumulation of reactive oxygen species (ROS). Endoplasmic reticulum (ER) stress was increased via unfolded protein response stimulation, which induced autophagy. N-acetylcysteine, a ROS scavenger, diminished ER stress and autophagy induction effects. This result indicated that Agelas extracts may sensitize HCC cells to IR via ROS overproduction in vitro. Our findings suggest that the Agelas sp. may have potential utility in radiosensitizer development.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Acetilcisteína/metabolismo , Agelas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Extratos Celulares/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Micronésia , Poríferos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Mar Drugs ; 15(11)2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29117128

RESUMO

The marine sponge genus Agelas comprises a rich reservoir of species and natural products with diverse chemical structures and biological properties with potential application in new drug development. This review for the first time summarized secondary metabolites from Agelas sponges discovered in the past 47 years together with their bioactive effects.


Assuntos
Agelas/metabolismo , Produtos Biológicos/metabolismo , Agelas/química , Animais , Organismos Aquáticos , Produtos Biológicos/química
3.
Bioorg Med Chem Lett ; 27(10): 2207-2209, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28389151

RESUMO

Agelasine G (1), a known bromine-containing diterpene alkaloid, was isolated as a new type of protein tyrosine phosphatase (PTP) 1B inhibitor together with ageline B (2), an inactive debromo-derivative of 1, from the marine sponge Agelas nakamurai collected at Iriomote Island in Okinawa, Japan. Further biological evaluations revealed that compound 1 exhibited selective inhibitory activity against PTP1B over T-cell PTP and CD45 phosphatase. Compound 1 also enhanced the insulin-stimulated phosphorylation levels of Akt in Huh-7 cells more strongly than compound 2. The results obtained in this study suggest that compound 1 activates the insulin signaling pathway by inhibiting PTP1B activity.


Assuntos
Agelas/química , Alcaloides/química , Diterpenos/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Agelas/metabolismo , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Diterpenos/toxicidade , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/toxicidade , Humanos , Insulina/metabolismo , Japão , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fosforilação/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Pirróis/química , Transdução de Sinais/efeitos dos fármacos
4.
Angew Chem Int Ed Engl ; 51(20): 4877-81, 2012 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-22473581

RESUMO

Game-SET-match: Pyrrole aminoimidazole alkaloids (PAIs) are metabiosynthesized from chlorinated analogues of oroidin by cell-free enzyme preparations from PAI-producing sponges. Evidence and implications for the biosynthesis of PAIs include putative single-electron transfers (SETs) that promote C-C bond-forming reactions of precursors.


Assuntos
Agelas/metabolismo , Alcaloides/biossíntese , Imidazóis/metabolismo , Poríferos/metabolismo , Pirróis/metabolismo , Agelas/química , Alcaloides/síntese química , Animais , Imidazóis/síntese química , Poríferos/química , Pirróis/síntese química
5.
Bioorg Med Chem ; 18(3): 1297-311, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20061160

RESUMO

Chemical investigation of Indonesian marine sponges Agelas linnaei and A. nakamurai afforded 24 alkaloid derivatives representing either bromopyrrole or diterpene alkaloids. A. linnaei yielded 16 bromopyrrole alkaloids including 11 new natural products with the latter exhibiting unusual functionalities. The new compounds include the first iodinated tyramine-unit bearing pyrrole alkaloids, agelanesins A-D. These compounds exhibited cytotoxic activity against L5178Y mouse lymphoma cells with IC(50) values between 9.25 and 16.76 muM. Further new compounds include taurine acid substituted bromopyrrole alkaloids and a new dibromophakellin derivative. A. nakamurai yielded eight alkaloids among them are three new natural products. The latter include the diterpene alkaloids (-)-agelasine D and its oxime derivative and the new bromopyrrole alkaloid longamide C. (-)-Agelasine D and its oxime derivative exhibited cytotoxicity against L5178Y mouse lymphoma cells (IC(50) 4.03 and 12.5 microM, respectively). Furthermore, both agelasine derivatives inhibited settling of larvae of Balanus improvisus in an anti-fouling bioassay and proved to be toxic to the larvae. (-)-Agelasine D inhibited the growth of planktonic forms of biofilm forming bacteria S. epidermidis (MIC<0.0877 microM) but did not inhibit biofilm formation whereas the oxime derivative showed the opposite activity profile and inhibited only biofilm formation but not bacterial growth. The structures of the isolated secondary metabolites were elucidated based on extensive spectroscopic analysis involving one- and two-dimensional NMR as well as mass spectrometry and comparison with literature data.


Assuntos
Agelas/química , Alcaloides/química , Alcaloides/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Citotoxinas/química , Citotoxinas/farmacologia , Agelas/metabolismo , Alcaloides/isolamento & purificação , Animais , Antibacterianos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Compostos de Bromo/química , Compostos de Bromo/isolamento & purificação , Compostos de Bromo/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Indonésia , Larva/efeitos dos fármacos , Camundongos , Pirróis/química , Pirróis/isolamento & purificação , Pirróis/farmacologia , Staphylococcus epidermidis/efeitos dos fármacos , Thoracica/efeitos dos fármacos
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