Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
1.
J Org Chem ; 88(23): 16649-16654, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37967371

RESUMO

Herein, we present a novel method for the N-arylation of amino acid esters using α-bromoacetaldehyde acetal and acetoacetate via an I2-mediated metal-free benzannulation strategy, which disclosed the first synthetic application of N-arylation of amino acids using nonaromatic building blocks. The synthesized N-arylated amino acid derivatives were found to possess promising selective inhibition against human hepatocellular liver carcinoma cells, human melanoma cells, and human normal liver cells, with an IC50 value as low as 16.79 µg·mL-1.


Assuntos
Aminoácidos , Ésteres , Humanos , Aminoácidos/química , Ésteres/química , Metais
2.
Molecules ; 28(2)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36677698

RESUMO

Two new napyradiomycins derivatives, napyradiomycin A4 (1) and A80915 H (2), along with five known ones, were isolated from the ethyl acetate extract of fermentation culture of Streptomyces kebangsaanensis WS-68302. Their structures were elucidated by extensive spectroscopic analysis, including HR-MS, 1D and 2D NMR, CD spectrum, as well as comparison with literature data. Compound 1 exhibited significant antiviral activity against PRV (Pseudorabies virus) with an IC50 value of 2.056 µM and therapeutic ratio at 14.98, suggesting that it might have potential for development of an antiviral agent. Moreover, compound 1 displayed the strongest inhibition against PRV protein among the tested napyradiomycins in the indirect immunofuorescence assay. Compounds 3 and 4 showed higher activities against swine pathogenic Streptococcus suis than the positive control penicillin G sodium salt, with MIC values of 3.125 and 6.25 µg/mL, respectively. Compounds 1 and 3-6 exhibited moderate antibacterial activity against the swine pathogenic Erysipelothrix rhusiopathiae, with MIC values ranging from 25 to 50 µg/mL.


Assuntos
Antibacterianos , Streptomyces , Animais , Suínos , Antibacterianos/química , Streptomyces/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana
3.
Molecules ; 28(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36985662

RESUMO

Two series of novel steroidal[17,16-d]pyrimidines derived from natural epiandrosterone and androsterone were designed and synthesized, and these compounds were screened for their potential anticancer activities. The preliminary bioassay indicated that some of these prepared compounds exhibited significantly good cytotoxic activities against human gastric cancer (SGC-7901), lung cancer (A549), and hepatocellular liver carcinoma (HepG2) cell lines compared with 5-fluorouracil (5-FU), epiandrosterone, and androsterone. Especially the respective pairs from epiandrosterone and androsterone showed significantly different inhibitory activities, and the possible configuration-activity relationships have also been summarized and discussed based on kinase assay and molecular docking, which indicated that the inhibition activities of these steroidal[17,16-d]pyrimidines might obviously be affected by the configuration of the hydroxyl group in the part of the steroidal scaffold.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Androsterona/farmacologia , Pirimidinas/farmacologia , Simulação de Acoplamento Molecular , Proliferação de Células , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Esteroides/farmacologia , Fluoruracila/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade
4.
Molecules ; 27(5)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35268580

RESUMO

Primary arylsulfonamide functional groups feature prominently in diverse pharmaceuticals. However, natural arylsulfonamides are relatively infrequent. In this work, two novel arylsulfonamide natural products were first synthesized, and then a series of novel molecules derived from natural arylsulfonamides were designed and synthesized, and their in vitro cytotoxic activities against A875, HepG2, and MARC145 cell lines were systematically evaluated. The results indicate that some of these arylsulfonamide derivatives exhibit significantly good cytotoxic activity against the tested cell lines compared with the control 5-fluorouracil (5-FU), such as compounds 10l, 10p, 10q, and 10r. In particular, the potential molecule 10q, containing a carbazole moiety, exhibited the highest inhibitory activity against all tested cell lines, with IC50 values of 4.19 ± 0.78, 3.55 ± 0.63, and 2.95 ± 0.78 µg/mL, respectively. This will offer the potential to discover novel drug-like compounds from the sparsely populated area of natural products that can lead to effective anticancer agents.


Assuntos
Antineoplásicos
5.
Bioorg Chem ; 113: 104991, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34051416

RESUMO

Carbazole alkaloids is an important class of natural products with diverse biological functions. So, the aim of this article is to explore new chemical entities containing carbazole scaffold as potential novel cytotoxic agents based on our developed three-component indole-to-carbazole reaction. Two series of carbazole derivatives were designed and synthesized, and their in vitro cytotoxic activities against three cell lines (A875, HepG2, and MARC145) were evaluated. The results indicated that some of these carbazole derivatives exhibited significantly good cytotoxic activities against tested cell lines compared with the control 5-fluorouracil (5-FU). Especially, carbazole acylhydrazone compounds 7g and 7p displayed high inhibitory activity on cancer cells, but almost no activity on normal cells. Further analysis of induced apoptosis for potential compounds indicated that the potential antitumor agents induced cell death in A875 cells at least partly (initially) by apoptosis, which might be used as promising lead scaffold for discovery of novel carbazole-type cytotoxic agents.


Assuntos
Antineoplásicos/farmacologia , Carbazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Carbazóis/síntese química , Carbazóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
6.
Bioorg Med Chem Lett ; 30(13): 127245, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32389528

RESUMO

Aryl-oxazole alkaloids are an important class of heterocyclic natural products, and which has been demonstrated to exhibit broad biological functions. During the course of our research for highly active compounds from natural products, the natural hinduchelins A-D with typical aryl-oxazole unit have been synthesized and investigated. So, in order to develop highly potential functional molecules, a series of novel sulfur-containing aryl-oxazole compounds derived from natural hinduchelins was designed and synthesized, and their in vitro fungicidal activities against four common plant pathogenic fungi (oomycetes Phytophthora capsici, ascomycetes Sclerotinia sclerotiorum, deuteromycetes Botrytis cinerea and basidiomycetes Rhizoctonia solani) were evaluated, the results demonstrated that compounds 7b and 7c displayed good selectivity and specificity in vitro against basidiomycetes R. solani. In addition, the in vivo antifungal activities also indicated compounds 7b and 7c can protect the horsebean against infection by R. solani, and the possible mechanism of antifungal action for these compounds has also been investigated.


Assuntos
Antifúngicos/farmacologia , Oxazóis/farmacologia , Rhizoctonia/efeitos dos fármacos , Sulfetos/farmacologia , Sulfonas/farmacologia , Antifúngicos/síntese química , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Oxazóis/síntese química , Doenças das Plantas/prevenção & controle , Sulfetos/síntese química , Sulfonas/síntese química , Vicia faba/microbiologia
7.
Bioorg Med Chem Lett ; 30(12): 127193, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32334913

RESUMO

This study aims to investigate active phytochemicals isolated from Pyrola incarnata Fisch. (P. incarnata) and their protection against neuroinflammation induced by LPS. Betulin, accompanied with other 9 compounds, were isolated from P. incarnata and elucidated by spectroscopic analysis (1H-, 13C NMR). ELISA kits and the measurement of NO production based on Griess reaction showed that betulin (5) (250 µg/mL) could suppress LPS-induced activation of microglial cell BV-2 better than others by inhibiting inflammatory cytokines (TNF-α, IL-6, IL-1ß) expression and NO production. With the guidance of computer-aided drug design and the analysis of biological experiment, we demonstrated betulin could reduce LPS-induced iNOS expression, prevent JNKs pathways, and down-regulate the phosphorylation levels of NF-κB/p65. In conclusion, betulin isolated from P. incarnata possessed outstanding anti-neuroinflammation potential, presumably related to iNOS expression, JNKs and NF-κB/p65 pathways. Therefore, Pyrola incarnata may be a valuable natural resource and betulin is a potential drug for the treatment of neurodegenerative disorders by inhibiting inflammatory mediators.


Assuntos
Desenho de Fármacos , Mediadores da Inflamação/farmacologia , Inflamação/tratamento farmacológico , Lipopolissacarídeos/antagonistas & inibidores , Pyrola/química , Triterpenos/farmacologia , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Mediadores da Inflamação/química , Mediadores da Inflamação/isolamento & purificação , Lipopolissacarídeos/farmacologia , Camundongos , Conformação Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação
8.
Org Biomol Chem ; 17(14): 3635-3639, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30916700

RESUMO

Oxazoles are an important class of biologically active metabolites from nature, and exhibit broad biological activities as the lead for drug discovery. Hinduchelins are a class of unusual natural products with an oxazole unit, isolated from Streptoalloteichus hindustanus, and with a potential iron-chelating ability. These compounds are the first identified naturally occurring unusual oxazole derivatives to possess a catechol unit. However, some of these compounds are not abundant in nature, and thus, the efficient syntheses of these compounds are advantageous in exploring their potential applications. This paper reports the efficient synthesis and bio-evaluation of hinduchelins A-D and their derivatives with convenient procedures and high yields.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Inseticidas/farmacologia , Oxazóis/farmacologia , Actinomycetales/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Afídeos/efeitos dos fármacos , Produtos Biológicos/síntese química , Produtos Biológicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Inseticidas/síntese química , Inseticidas/química , Testes de Sensibilidade Microbiana , Mariposas , Oxazóis/síntese química , Oxazóis/química
9.
J Enzyme Inhib Med Chem ; 34(1): 1607-1614, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31474167

RESUMO

Steroids are classes of natural products widely distributed in nature, which have been demonstrated to exhibit broad biological functions, and have also attracted increasing interest from bioorganic and pharmaceutical researches. In order to develop novel chemical entities as potential cytotoxic agents, a series of steroidal isatin conjugations derived from epiandrosterone and androsterone were efficiently prepared and characterized, and all these obtained compounds were screened for their potential cytotoxic activities. The preliminary bioassay indicated that most of the newly synthesized compounds exhibited good cytotoxic activities against human gastric cancer (SGC-7901), melanoma (A875), and hepatocellular liver carcinoma (HepG2) cell lines compared with 5-fluorouracil (5-FU), which might be considered as promising scaffold for further development of potential anticancer agents.


Assuntos
Androsterona/química , Antineoplásicos Fitogênicos/farmacologia , Produtos Biológicos/farmacologia , Isatina/farmacologia , Esteroides/farmacologia , Androsterona/análogos & derivados , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isatina/síntese química , Isatina/química , Estrutura Molecular , Esteroides/síntese química , Esteroides/química , Relação Estrutura-Atividade
10.
J Nat Prod ; 81(6): 1405-1410, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29786436

RESUMO

Three new eremophilane sesquiterpenes, dendryphiellins H-J (1-3), and three new phthalide natural products (4-6) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Dendryphiellin I (2) showed cytotoxic and antibacterial activities against five cancer cell lines (IC50 1.4 to 4.3 µM) and three bacterial species (MIC 1.5 to 13 µg/mL), respectively. Dendryphiellin J (3), a rare naturally occurring aldoxime analogue, displayed cytotoxicities against ACHN and HepG-2 cells with IC50 values of 3.1 and 5.9 µM, respectively. Further studies indicated that 3 induced apoptosis in ACHN cells in a dose- and time-dependent manner.


Assuntos
Antibacterianos/química , Ascomicetos/química , Citotoxinas/química , Sesquiterpenos/química , Antibacterianos/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Linhagem Celular Tumoral , Citotoxinas/farmacologia , Células Hep G2 , Humanos , Sesquiterpenos/farmacologia
11.
Bioorg Med Chem Lett ; 26(14): 3263-3270, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27262600

RESUMO

A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50 values of 2.21µg/mL, 1.67µg/mL and 1.11µg/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide-hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest.


Assuntos
Antineoplásicos/farmacologia , Hidrazinas/farmacologia , Hidrazonas/farmacologia , Tiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hidrazinas/química , Hidrazonas/química , Estrutura Molecular , Relação Estrutura-Atividade , Tiazóis/química
12.
Arch Virol ; 161(11): 3061-72, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27518401

RESUMO

The antiviral activity of dehydroepiandrosterone (DHEA) and 21 synthetic derivatives against influenza A virus (IAV) replication was investigated in vitro in cell culture. Our results revealed that three DHEA analogues were potent inhibitors of IAV multiplication in MDCK cells and mainly blocked the post-attachment stage of viral infection. Among these derivatives, one containing a 2-OH-Ph moiety (3i) exhibited the best inhibitory effects against H1N1 and H3N2 IAV in a dose-dependent manner. Moreover, treatment with compound 3i decreased progeny virus yields, viral RNA synthesis and protein expression. Orally administered compound 3i at 25 or 50 mg/kg/day for 5 days protected mice from lethal A/FM/1/47 (H1N1) challenge by reducing the viral titers in the lungs and promoting survival of infected mice. Our results suggest that DHEA-dihydrazone derivatives may provide promising lead scaffolds for further design and synthesis of potential antiviral agents.


Assuntos
Antivirais/farmacologia , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/fisiologia , Animais , Antivirais/uso terapêutico , Desidroepiandrosterona/uso terapêutico , Modelos Animais de Doenças , Cães , Humanos , Células Madin Darby de Rim Canino , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/tratamento farmacológico , Análise de Sobrevida , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
13.
Bioorg Med Chem Lett ; 25(24): 5772-6, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26546214

RESUMO

A series of novel acylhydrazone derivatives were designed, synthesized and evaluated for their potential cytotoxic effects against human cancer cell lines. The preliminary results indicated that some of the obtained compounds (such as 8b, 13c) exhibited good to moderate cytotoxic activities against human HepG2, Huh-7, and BCG-823 cell lines. Especially, compounds 8c and 8e presented obviously selective cytotoxic activities against Huh-7 in vitro (8c, IC50=7.74±2.18µg/mL; 8e, IC50=4.46±1.05µg/mL) compared to 5-FU (IC50=10.41±3.41µg/mL). The highly potential compounds to induce apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compounds 8b and 13c were further evaluated using Annexin V-FITC/propidium iodide dual staining assay.


Assuntos
Antineoplásicos/síntese química , Hidrazonas/química , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/toxicidade , Células Hep G2 , Humanos , Hidrazonas/síntese química , Hidrazonas/toxicidade
14.
Bioorg Med Chem Lett ; 25(20): 4628-31, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26320625

RESUMO

A series of isatin-dehydroepiandrosterone hybrids were synthesised via a convenient condensation procedure, and which were evaluated for their potential anticancer activities. The preliminary assays indicated that some of the newly obtained compounds exhibited good antitumor activities against human hepatocellular liver carcinoma (HepG2), heptoma (Huh-7), melanoma (A875) and 5-fluorouracil-resistant human hepatocellular carcinoma (BEL-7402/5-FU) cell lines compared with 5-fluorouracil (5-FU), which might be considered as promising lead scaffold for further design and synthesis of highly potential anticancer agents.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Desidroepiandrosterona/farmacologia , Descoberta de Drogas , Isatina/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desidroepiandrosterona/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isatina/química , Estrutura Molecular , Relação Estrutura-Atividade
15.
Virol J ; 11: 195, 2014 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-25410379

RESUMO

BACKGROUND: The pimprinine family of compounds represent very important and promising microbial metabolites for drug discovery. However, their ability in inhibiting viral infections has not yet been tested. METHODS: The antiviral activity of the pimprinine family of compounds was evaluated by determining the cytopathic effect (CPE), cell viability or plaque-forming unit (PFU), and virus yield. The mechanism of action against EV71 was determined from the virucidal activity, and effective stage and time-of-addition assays. The effects on EV71 replication were evaluated further by determining viral RNA synthesis, protein expression and cells apoptosis using the SYBR Green assays, immunofluorescence assays and flow cytometric assays, respectively. RESULTS: Pimprinethine, WS-30581 A and WS-30581 B inhibited EV71-induced CPE, reduced progeny EV71 yields, as well as prevented EV71-induced apoptosis in human rhabdomyosarcoma (RD) cells. These compounds were found to target the early stages of the EV71 replication in cells including viral RNA replication and protein synthesis. They also showed antiviral activity against ADV-7, and were slightly active against CVB3, HSV-1 and H1N1 with a few exceptions. Pimprinine was slightly active or inactive against all the viruses tested. The mechanisms by which these compounds act against the viruses tested may be similar to that demonstrated for EV71. CONCLUSION: The data described herein demonstrate that the pimprinine family of compounds are inhibitors effective against the replication of EV71 and ADV-7, so they might be feasible therapeutic agents for the treatment of viral infections.


Assuntos
Antivirais/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Enterovirus Humano A/fisiologia , Oxazóis/farmacologia , Adenoviridae/efeitos dos fármacos , Adenoviridae/fisiologia , Antivirais/isolamento & purificação , Efeito Citopatogênico Viral/efeitos dos fármacos , Herpesvirus Humano 1 , Viabilidade Microbiana/efeitos dos fármacos , Oxazóis/isolamento & purificação , Streptomyces/química , Ensaio de Placa Viral , Replicação Viral/efeitos dos fármacos
16.
Bioorg Med Chem Lett ; 24(8): 1907-11, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24684840

RESUMO

A series of multisubstituted indole-acrylonitrile hybrids were designed, synthesized and evaluated for their potential cytotoxic activities. The bio-evaluation results indicated that some of the target compounds (such as 3a, 3f, 3k, 3n) exhibited good to moderate cytotoxic effect on HepG2, BCG-823, BEL-7402, and HL-7702 cell lines. Especially, the compounds 3a and 3k also exhibited high cytotoxic activities (3a, 19.38±3.38 µM; 3k, 15.43±3.54 µM) against the BEL-7402 cell line resistant to Taxol (>25µM) and 5-FU (>500 µM), which might be developed as novel lead scaffold for potential anticancer agents.


Assuntos
Acrilonitrila , Antineoplásicos , Citotoxinas , Indóis , Acrilonitrila/química , Acrilonitrila/toxicidade , Antineoplásicos/química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/química , Citotoxinas/toxicidade , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Indóis/química , Indóis/toxicidade , Concentração Inibidora 50 , Estrutura Molecular
17.
Chem Pharm Bull (Tokyo) ; 62(1): 118-21, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24390501

RESUMO

Four new alkylated anthraquinone analogues (1-4) were isolated from a soil actimomycete Streptomyces sp. WS-13394. The structures of compounds 1-4 were elucidated to be 1,4,6-trihydroxy-8-alkylanthraquinones by means of spectroscopic methods, including UV, one dimensional (1D), 2D-NMR and MS spectrometry. All compounds showed activities against BGC-823 and MCF-7 with IC50 from 0.99 to 3.54 µg/mL, while 2 exhibited cytotoxicity against HepG2, A875, BGC-823 and MCF-7 with IC50 2.29, 4.90, 0.99, and 1.66 µg/mL, respectively.


Assuntos
Actinobacteria/química , Antraquinonas/química , Antraquinonas/farmacologia , Solo/química , Streptomyces/química , Alquilação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células Hep G2 , Humanos , Concentração Inibidora 50 , Células MCF-7
18.
Molecules ; 19(7): 8949-64, 2014 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-24979400

RESUMO

Enterovirus 71 (EV71) is a notable causative agent of hand, foot, and mouth disease in children, which is associated with an increased incidence of severe neurological disease and death, yet there is no specific treatment or vaccine for EV71 infections. In this study, the antiviral activity of gramine and 21 gramine derivatives against EV71 was investigated in cell-based assays. Eighteen derivatives displayed some degree of inhibitory effects against EV71, in that they could effectively inhibit virus-induced cytopathic effects (CPEs), but the anti-EV71 activity of the lead compound gramine was not observed. Studies on the preliminary modes of action showed that these compounds functioned by targeting the early stage of the EV71 lifecycle after viral entry, rather than inactivating the virus directly, inhibiting virus adsorption or affecting viral release from the cells. Among these derivatives, one (compound 4s) containing pyridine and benzothiazole units showed the most potency against EV71. Further studies demonstrated that derivative 4s could profoundly inhibit viral RNA replication, protein synthesis, and virus-induced apoptosis in RD cells. These results indicate that derivative 4s might be a feasible therapeutic agent against EV71 infection and that these gramine derivatives may provide promising lead scaffolds for the further design and synthesis of potential antiviral agents.


Assuntos
Antivirais/farmacologia , Enterovirus Humano A/fisiologia , Furanos/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/química , Apoptose , Chlorocebus aethiops , Enterovirus Humano A/efeitos dos fármacos , Furanos/química , Concentração Inibidora 50 , Células Vero
19.
Bioorg Med Chem Lett ; 23(18): 5131-4, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23920438

RESUMO

A series of novel cycloalkylthiophene-imine derivatives containing benzothiazole unit were designed, synthesized and evaluated for their anti-viral activities. The bio-evaluation results indicated that some of the target compounds (such as 5g, 5i, 5u) exhibited good to moderate antiviral effect on CVB5, ADV7 and EV71 viruses, however, these compounds did not have inhibition activity against H1N1 virus. Especially, the compounds 4c and 4d also exhibited high antiviral activities, which provide a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration of active pharmacophores.


Assuntos
Antivirais/farmacologia , Benzotiazóis/química , Iminas/farmacologia , Tiofenos/farmacologia , Vírus/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Iminas/síntese química , Iminas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/química , Vírus/crescimento & desenvolvimento
20.
J Neurosci Res ; 90(4): 816-30, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22213141

RESUMO

The peripheral taste system presents an excellent model for studying the consequences of neural injury, for the damaged nerve and sensory cells and the neighboring, intact neural cells. Sectioning a primary afferent nerve, the chorda tympani (CT), rapidly recruits neutrophils to both sides of the tongue. The bilateral neutrophil response induces transient functional deficits in the intact CT. Normal function is subsequently restored as macrophages respond to injury. We hypothesized that macrophages produce the proinflammatory cytokine interleukin (IL)-1, which contributes to the maintenance of normal taste function after nearby injury. We demonstrate that IL-1ß protein levels are significantly increased on the injured side of the tongue at day 2 after injury. Dietary sodium deficiency, a manipulation that prevents macrophage recruitment, inhibits the elevation in IL-1ß. IL-1ß was expressed in several cell populations, including taste receptor cells and infiltrating neutrophils and macrophages. To test whether IL-1 modulates taste function after injury, we blocked signaling with an IL-1 receptor antagonist (IL-1 RA) and recorded taste responses from the intact CT. This treatment inhibited the bilateral macrophage response to injury and impaired taste responses in the intact CT. Cytokine actions in the taste system are largely unstudied. These results demonstrate that IL-1 has a beneficial effect on taste function after nearby injury, in contrast to its detrimental role in the injured central nervous system.


Assuntos
Nervo da Corda do Tímpano/patologia , Doenças do Nervo Facial/patologia , Doenças do Nervo Facial/fisiopatologia , Regulação da Expressão Gênica/fisiologia , Interleucina-1beta/metabolismo , Paladar/fisiologia , Análise de Variância , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ectodisplasinas/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Doenças do Nervo Facial/imunologia , Feminino , Lateralidade Funcional , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Leucócitos/efeitos dos fármacos , Macrófagos/metabolismo , Neutrófilos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-1/antagonistas & inibidores , Receptores de Interleucina-1/metabolismo , Sódio na Dieta/administração & dosagem , Sódio na Dieta/farmacologia , Papilas Gustativas/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA