Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 74
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Bioorg Med Chem Lett ; 35: 127783, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33422607

RESUMO

A new unique sesquiterpene lactone, bicyclolamellolactone A (1), was isolated together with two known monocyclofarnesol-type sesquiterpenes, lamellolactones A (2) and B (3), from the Indonesian marine sponge Lamellodysidea sp. (cf. L. herbacea). The planar structure of 1 was assigned based on its spectroscopic data (1D and 2D NMR, HRESIMS, UV, and IR spectra). The relative and absolute configuration of 1 was determined by comparison of its calculated and experimental electronic circular dichroism spectra in combination with NOESY correlations. Compounds 1-3 inhibited bone morphogenic protein (BMP)-induced alkaline phosphatase activity in mutant BMP receptor-carrying C2C12 cells with IC50 values of 51, 4.6, and 20 µM, respectively.


Assuntos
Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Lactonas/farmacologia , Osteoblastos/efeitos dos fármacos , Poríferos/química , Sesquiterpenos/farmacologia , Fosfatase Alcalina/antagonistas & inibidores , Fosfatase Alcalina/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Indonésia , Lactonas/química , Lactonas/isolamento & purificação , Camundongos , Estrutura Molecular , Osteoblastos/metabolismo , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade
2.
Mar Drugs ; 18(12)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33265937

RESUMO

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder with heterotopic ossification (HO) in soft tissues. The abnormal activation of bone morphogenetic protein (BMP) signaling by a mutant activin receptor-like kinase-2 (ALK2) leads to the development of HO in FOP patients, and, thus, BMP signaling inhibitors are promising therapeutic applications for FOP. In the present study, we screened extracts of 188 Indonesian marine invertebrates for small molecular inhibitors of BMP-induced alkaline phosphatase (ALP) activity, a marker of osteoblastic differentiation in a C2C12 cell line stably expressing ALK2(R206H) (C2C12(R206H) cells), and identified five marine sponges with potent ALP inhibitory activities. The activity-guided purification of an EtOH extract of marine sponge Dysidea sp. (No. 256) resulted in the isolation of dysidenin (1), herbasterol (2), and stellettasterol (3) as active components. Compounds 1-3 inhibited ALP activity in C2C12(R206H) cells with IC50 values of 2.3, 4.3, and 4.2 µM, respectively, without any cytotoxicity, even at 18.4-21.4 µM. The direct effects of BMP signaling examined using the Id1WT4F-luciferase reporter assay showed that compounds 1-3 did not decrease the reporter activity, suggesting that they inhibit the downstream of the Smad transcriptional step in BMP signaling.


Assuntos
Fosfatase Alcalina/antagonistas & inibidores , Diferenciação Celular/efeitos dos fármacos , Dysidea/metabolismo , Inibidores Enzimáticos/farmacologia , Mioblastos Esqueléticos/efeitos dos fármacos , Miosite Ossificante/tratamento farmacológico , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Esteróis/farmacologia , Tiazóis/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Proteína Morfogenética Óssea 4/toxicidade , Linhagem Celular , Inibidores Enzimáticos/isolamento & purificação , Indonésia , Camundongos , Estrutura Molecular , Mioblastos Esqueléticos/metabolismo , Mioblastos Esqueléticos/patologia , Miosite Ossificante/metabolismo , Miosite Ossificante/patologia , Osteoblastos/metabolismo , Osteoblastos/patologia , Esteróis/isolamento & purificação , Relação Estrutura-Atividade , Tiazóis/isolamento & purificação
3.
Bioorg Med Chem Lett ; 30(17): 127375, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739000

RESUMO

Two new trichothecene sesquiterpenes, trichobreols D (1) and E (2), were isolated from the culture broth of marine-derived Trichoderma cf. brevicompactum together with trichobreol A (3). The structures of 1 and 2 were assigned on the basis of their spectroscopic data. Compound 1 inhibited the growth of two yeast-like fungi, Candida albicans and Cryptococcus neoformans, with equivalent MIC values (6.3 µg/mL), while 2 gave MIC values of 12.5 and 25 µg/mL, respectively. The antifungal activities of five semisynthetic derivatives (4-8) prepared from 3 were evaluated and compared to investigate the preliminary structure-activity relationship.


Assuntos
Antifúngicos/química , Sesquiterpenos/química , Trichoderma/química , Tricotecenos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Conformação Molecular , Rodófitas/microbiologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade , Trichoderma/metabolismo , Tricotecenos/isolamento & purificação , Tricotecenos/farmacologia
4.
J Antibiot (Tokyo) ; 73(8): 559-567, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32427947

RESUMO

The marine-derived fungus Trichoderma sp. TPU199 (cf. Trichoderma brevicompactum) produces pretrichodermamide A (1) and gliovirin (2), which possess a rare type of epipolythiodiketopiperazine (ETP) structure with a disulfide bridge between the α- and ß-positions of two amino acid residues. We previously reported that this strain gave the halogenated ETPs, DC1149B (4), DC1149R (6), and iododithiobrevamide (7), when fermented with sodium halides (NaCl, NaBr, and NaI). Further analyses of the metabolites obtained under NaI-containing culture conditions resulted in the isolation of two new ETP derivatives (11 and 12) and three new trichothecene sesquiterpenes (13-15). The structures of 11 and 12, including their absolute configurations, were elucidated based on spectroscopic data for 11 and 12 and comparisons with those for 1 and related compounds, revealing that 11 was an epimer of 1 at the C-5 position and 12 was a trithio-derivative of 11. The structures of 13-15 were established by analyzing their 1D and 2D NMR data. The absolute configurations of 13-15 were assigned by comparing their experimental electronic circular dichroism (ECD) spectra with the calculated ECD spectrum of 13.


Assuntos
Organismos Aquáticos/química , Hypocreales/química , Piperazinas/química , Tricotecenos/química , Dicroísmo Circular/métodos , Fermentação/fisiologia , Sesquiterpenos/química
5.
J Asian Nat Prod Res ; 22(8): 754-761, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31311336

RESUMO

A benzyl-α-pyrone metabolite, streptpyrone A (1), was obtained together with three known isoflavonoids, daidzein-7-O-α-l-rhamnoside (2), genistein-7-O-α-l-rhamnoside (3), and daidzein (4), from the culture broth of an Indonesian actinomycete Streptomyces sp. TPU1401A. The structure of 1, elucidated based on its spectroscopic data, has been reported as a synthetic compound. However, this is the first report of the isolation of 1 as a metabolite of microbial origin. Strain TPU1401A exhibited the ability to transform the isoflavone aglycones 4 and genistein (5) into the 7-O-glycosides 2 and 3, respectively. Compounds 2 and 3 promoted the growth of strain TPU1401A more effectively than compounds 4 and 5. These results suggest that strain TPU1401A utilizes isoflavone glycosides to promote growth by transforming isoflavones through microbial glycosidation.


Assuntos
Isoflavonas , Streptomyces , Genisteína , Indonésia , Estrutura Molecular , Pironas
6.
Bioorg Med Chem Lett ; 29(16): 2283-2285, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31253530

RESUMO

The effects of 14 sesquiterpene hydroquinones, including 8 marine sponge-derived avarols (1-8) and 6 semisynthetic derivatives (9-14), on lipid droplet accumulation and neutral lipid synthesis in Chinese hamster ovary (CHO) K1 cells were investigated. In intact CHO-K1 cell assays, avarol (1) markedly decreased the number and size of lipid droplets in CHO-K1 cells and exhibited the most potent inhibitory activity on the synthesis of cholesteryl ester (CE) and triglyceride (TG) with IC50 values of 5.74 and 6.80 µM, respectively. In enzyme assays, sterol O-acyltransferase (SOAT), the final enzyme involved in CE biosynthesis, and diacylglycerol acyltransferase (DGAT), the final enzyme involved in TG biosynthesis, were inhibited by 1 with IC50 values of 7.31 and 20.0 µM, respectively, which correlated well with those obtained in the intact cell assay. These results strongly suggest that 1 inhibited SOAT and DGAT activities in CHO-K1 cells, leading to a reduction in the accumulation of CE and TG in lipid droplets.


Assuntos
Lipídeos/antagonistas & inibidores , Sesquiterpenos/farmacologia , Animais , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Gotículas Lipídicas/efeitos dos fármacos , Lipídeos/síntese química , Lipídeos/química , Estrutura Molecular , Tamanho da Partícula , Poríferos , Sesquiterpenos/síntese química , Sesquiterpenos/química , Relação Estrutura-Atividade , Propriedades de Superfície
7.
Chem Pharm Bull (Tokyo) ; 66(6): 682-687, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29863070

RESUMO

Two sesquiterpene lactones with the (9R)-eudesman-9,12-olide framework, wedelolides I and J, have been isolated together with five eudesmanolide sesquiterpenes and twelve ent-kaurene diterpenes from the aerial parts of Indonesian Wedelia prostrata. The absolute configurations of wedelolides I and J, proposed in the previous communication, were proven by comparing their experimental Electronic Circular Dichroism (ECD) spectra with the calculated ECD spectrum of wedelolide I. The phytochemical study on the aerial parts of Okinawan Wedelia chinensis led to the isolation of three other eudesmanolide sesquiterpenes in addition to the three sesquiterpenes and eleven diterpenes isolated from the Indonesian W. prostrata as above. However, the wedelolide derivatives found in the Indonesian plant were not detected. Among these compounds, most of the diterpenes inhibited protein tyrosine phosphatase (PTP) 1B activity, and a structure-activity relationship study revealed that the cinnamoyl group enhanced inhibitory activity. Therefore, two ent-kaurene derivatives with and without a cinnamoyl group were examined for the ability to accumulate phosphorylated-Akt (p-Akt) because PTP1B dephosphorylates signal transduction from the insulin receptor such as phosphorylated Akt, a key downstream effector. However, neither compound enhanced insulin-stimulated p-Akt levels in two human hepatoma cell lines (Huh-7 and HepG2) at non-cytotoxic doses.


Assuntos
Diterpenos/farmacologia , Inibidores Enzimáticos/farmacologia , Componentes Aéreos da Planta/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Wedelia/química , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Células Hep G2 , Humanos , Indonésia , Japão , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade
8.
J Antibiot (Tokyo) ; 71(8): 745-748, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29679041

RESUMO

A new polyenyl-α-pyrone polyketide, aspopyrone A (1), was isolated from a culture broth of Okinawan plant-associated Aspergillus sp. TMPU1623 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was assigned based on NMR experiments. Compound 1 exhibited protein tyrosine phosphatase (PTP) 1B and T-cell PTP (TCPTP) inhibitory activities with IC50 values of 6.7 and 6.0 µM, respectively.


Assuntos
Policetídeos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Pironas/antagonistas & inibidores , Aspergillus/metabolismo
9.
Bioorg Med Chem Lett ; 28(10): 1911-1914, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29631961

RESUMO

Callyspongiamides A (1) and B (2), two new sterol O-acyltransferase (SOAT) inhibitors, were isolated from the Indonesian marine sponge Callyspongia sp. together with a known congener, dysamide A (3). The structures of 1 and 2 were elucidated to be polychlorine-containing modified dipeptides based on their spectroscopic data. Compounds 1-3 inhibited both of the SOAT isozymes, SOAT1 and SOAT2, in cell-based and enzyme-based assays.


Assuntos
Callyspongia/química , Dipeptídeos/farmacologia , Inibidores Enzimáticos/farmacologia , Esterol O-Aciltransferase/antagonistas & inibidores , Animais , Callyspongia/metabolismo , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Ensaios Enzimáticos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Indonésia , Concentração Inibidora 50 , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Espectroscopia de Ressonância Magnética , Conformação Molecular , Esterol O-Aciltransferase/metabolismo
10.
J Nat Med ; 72(3): 779-783, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29508256

RESUMO

Cladosporamide A (1), a new protein tyrosine phosphatase (PTP) 1B inhibitor, was isolated together with a known prenylated flavanone derivative (2) from the culture broth of an Indonesian marine sponge-derived Cladosporium sp. TPU1507 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was elucidated based on 1D and 2D NMR data. Compound 1 modestly inhibited PTP1B and T-cell PTP (TCPTP) activities with IC50 values of 48 and 54 µM, respectively. The inhibitory activity of 2 against PTP1B (IC50 = 11 µM) was approximately 2-fold stronger than that against TCPTP (IC50 = 27 µM).


Assuntos
Cladosporium/química , Poríferos/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Animais , Indonésia , Proteína Tirosina Fosfatase não Receptora Tipo 1/uso terapêutico
11.
Phytochemistry ; 144: 106-112, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28917090

RESUMO

During the search for new protein tyrosine phosphatase (PTP) 1B inhibitors, EtOH extracts from the aerial parts of Lantana camara L. (lantana) collected at Manado (Indonesia) and two subtropical islands in Japan (Ishigaki and Iriomote Islands, Okinawa) exhibited potent inhibitory activities against PTP1B in an enzyme assay. Four previously undescribed oleanane triterpenes were isolated together with known triterpenes and flavones from the Indonesian lantana. The EtOH extracts of lantana collected in Ishigaki and Iriomote Islands exhibited different phytochemical profiles from each other and the Indonesian lantana. Triterpenes with a 24-OH group were isolated from the Indonesian lantana only. Five known triterpene compounds were detected in the Ishigaki lantana, and two oleanane triterpenes with an ether linkage between 3ß and 25 were the main components together with five known triterpenes as minor components in the Iriomote lantana. The structures of previously undescribed compounds were assigned on the basis of their spectroscopic data. Among the compounds obtained in this study, oleanolic acid exhibited the most potent activity against PTP1B, and is used as a positive control in studies on PTP1B.


Assuntos
Inibidores Enzimáticos/farmacologia , Lantana/química , Ácido Oleanólico/análogos & derivados , Componentes Aéreos da Planta/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Indonésia , Japão , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade
12.
Bioorg Med Chem Lett ; 27(15): 3503-3506, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28601525

RESUMO

Three new dimeric 3-alkyl pyridinium alkaloids, named haliclocyclamines A-C (1-3), were isolated together with five known congeners, cyclostellettamines A (4), B (5), C (6), E (7), and F (8), from the Indonesian marine sponge Haliclona sp. The structures of 1-3 were assigned based on their spectroscopic data (1D and 2D NMR, HRFABMS, ESIMS/MS, UV, and IR). Compounds 1-8 exhibited antimicrobial activities against Mycobacterium smegmatis with inhibition zones of 17, 10, 13, 14, 8, 8, 12, and 12mm, respectively, at 10µg/disc. Compounds 3 and 8 also modestly inhibited the activity of vaccinia H-1-related phosphatase (VHR), a dual-specificity phosphatase, at 17-18µM.


Assuntos
Alcaloides/farmacologia , Antibacterianos/farmacologia , Haliclona/química , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium smegmatis/efeitos dos fármacos , Compostos de Piridínio/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Indonésia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Compostos de Piridínio/química , Compostos de Piridínio/isolamento & purificação
14.
Chem Pharm Bull (Tokyo) ; 65(6): 586-588, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28566651

RESUMO

A new pyranonaphthoquinone derivative, named 4-oxo-rhinacanthin A (1), was isolated from the roots of the Indonesian Rhinacanthus nasutus together with two known congeners, rhinacanthin A (2) and 3,4-dihydro-3,3-dimethyl-2H-naphtho[2,3-b]pyran-5,10-dione (3). The structure of 1 was elucidated based on its spectroscopic data. The absolute configuration of 1 was assigned by comparing its experimental Electronic Circular Dichroism (ECD) spectrum with the calculated ECD spectrum. Compounds 2 and 3 inhibited the growth of Staphylococcus aureus with inhibition zones of 16 and 20 mm at 25 µg/disc, respectively. Compound 3 also exhibited inhibitory activity against Mycobacterium smegmatis (20 mm at 25 µg/disc).


Assuntos
Naftoquinonas/isolamento & purificação , Raízes de Plantas/química , Antibacterianos/farmacologia , Indonésia , Naftoquinonas/química
15.
J Nat Med ; 71(4): 776-779, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28550651

RESUMO

A new biphenyl ether derivative, 2-hydroxy-6-(2'-hydroxy-3'-hydroxymethyl-5-methylphenoxy)-benzoic acid (1), was isolated together with the known benzophenone derivative, monodictyphenone (2), from a culture broth of Indonesian ascidian-derived Penicillium albobiverticillium TPU1432 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was elucidated based on NMR experiments. Compound 2 exhibited moderate inhibitory activities against protein tyrosine phosphatase (PTP) 1B, T cell PTP (TCPTP), and CD45 tyrosine phosphatase (CD45), whereas compound 1 modestly inhibited CD45 activity.


Assuntos
Penicillium/química , Éteres Fenílicos/química , Animais , Indonésia , Estrutura Molecular
16.
J Nat Med ; 71(3): 531-536, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28364227

RESUMO

In the course of our studies on anti-mycobacterial substances from marine organisms, the known dimeric sphingolipid, leucettamol A (1), was isolated as an active component, together with the new bromopyrrole alkaloid, 5-bromophakelline (2), and twelve known congeners from the Indonesian marine sponge Agelas sp. The structure of 2 was elucidated based on its spectroscopic data. Compound 1 and its bis TFA salt showed inhibition zones of 12 and 7 mm against Mycobacterium smegmatis at 50 µg/disk, respectively, while the N,N'-diacetyl derivative (1a) was not active at 50 µg/disk. Therefore, free amino groups are important for anti-mycobacterial activity. This is the first study to show the anti-mycobacterial activity of a bisfunctionalized sphingolipid. Compound 13 exhibited weak PTP1B inhibitory activity (29% inhibition at 35 µM).


Assuntos
Agelas/química , Antibacterianos/farmacologia , Mycobacterium smegmatis/efeitos dos fármacos , Pirróis/isolamento & purificação , Esfingolipídeos/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Indonésia , Estrutura Molecular , Mycobacterium smegmatis/crescimento & desenvolvimento , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Pirróis/química , Pirróis/farmacologia , Esfingolipídeos/química , Esfingolipídeos/isolamento & purificação , Relação Estrutura-Atividade
17.
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
18.
Bioorg Med Chem Lett ; 27(5): 1159-1161, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28189419

RESUMO

Protein tyrosine phosphatase (PTP) 1B negatively regulates the insulin and leptin signaling pathways, and, thus, the clinical application of PTP1B inhibitors to the prevention and treatment of type 2 diabetes and obesity is expected. During our studies on PTP1B inhibitors, two furanosesterterpenes and a C21 furanoterpene were obtained as new types of PTP1B inhibitors from two Indonesian marine sponges. (7E, 12E, 20Z, 18S)-Variabilin (1) and (12E, 20Z, 18S)-8-hydroxyvariabilin (2) from Ircinia sp. and furospongin-1 (3) from Spongia sp. inhibited PTP1B activity with IC50 values of 1.5, 7.1, and 9.9µM, respectively. The inhibitory activity of compound 1 against T-cell PTP (TCPTP) was approximately 2-fold that against PTP1B, whereas the vaccinia H-1-related phosphatase (VHR) inhibitory effects of 1 were 4-fold weaker than that of its PTP1B inhibitory activity. Compounds 1-3 at 50µM did not show cytotoxicity against two human cancer cell lines, hepatoma Huh-7 and bladder carcinoma EJ-1. Compound 1 did not enhance the phosphorylation level of Akt, a key downstream effector of the cascade, in Huh-7 cells.


Assuntos
Inibidores Enzimáticos/farmacologia , Furanos/farmacologia , Poríferos/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteínas/farmacologia , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos Knockout , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética
19.
J Nat Prod ; 80(2): 499-502, 2017 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-28181805

RESUMO

Lissoclibadins, polysulfur aromatic alkaloids, were isolated from the Indonesian ascidian Lissoclinum cf. badium. Lissoclibadins 1 (1), 3 (2), 4 (3), 7 (4), 8 (5), and 14 (6) inhibited the growth of four human solid cancer cell lines: HCT-15 (colon adenocarcinoma), HeLa-S3 (cervix adenocarcinoma), MCF-7 (breast adenocarcinoma), and NCI-H28 (mesothelioma). Lissoclibadin 1 (1) exerted the most potent cytotoxic effects in vitro and mainly promoted apoptosis through an intrinsic pathway with the activation of a caspase-dependent pathway in HCT-15 cells. In vivo studies demonstrated that 1 suppressed tumor growth in nude mice carrying HCT-15 cells without significant secondary adverse effects. In conclusion, the results obtained in the present study demonstrate that 1 has potential as a chemotherapeutic candidate for preclinical investigations.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Urocordados/química , Adenocarcinoma , Alcaloides/química , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Feminino , Células HeLa , Humanos , Indonésia , Células MCF-7 , Camundongos , Camundongos Nus , Estrutura Molecular
20.
Bioorg Med Chem Lett ; 27(4): 999-1002, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28109786

RESUMO

During the search for protein tyrosine phosphatase 1B (PTP1B) inhibitors from marine organisms, the known tetramic acid derivative, melophlin C (1), was isolated as an active component together with the new nortriterpenoid saponin, sarasinoside S (2), and three homologues: sarasinosides A1 (3), I1 (4), and J (5), from the Indonesian marine sponge Petrosia sp. The structure of 2 was elucidated on the basis of its spectroscopic data. Compound 1 inhibited PTP1B activity with an IC50 value of 14.6µM, while compounds 2-5 were not active at 15.2-16.0µM. This is the first study to report the inhibitory effects of a tetramic acid derivative on PTP1B activity.


Assuntos
Inibidores Enzimáticos/farmacologia , Glicosídeos/farmacologia , Petrosia/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Pirrolidinonas/farmacologia , Triterpenos/farmacologia , Animais , Inibidores Enzimáticos/química , Glicosídeos/química , Humanos , Concentração Inibidora 50 , Biologia Marinha , Pirrolidinonas/química , Triterpenos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...