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1.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873151

RESUMO

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.


Assuntos
Antivirais/administração & dosagem , Azidas/administração & dosagem , COVID-19/tratamento farmacológico , Desoxicitidina/análogos & derivados , SARS-CoV-2/metabolismo , Timo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Coronavirus Humano OC43/metabolismo , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Timo/metabolismo , Timo/virologia
2.
Org Lett ; 21(17): 7089-7093, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31456408

RESUMO

A highly efficient method for the enantioselective build of spiro[1-indanone-5,2'-γ-butyrolactones] has been developed through the tandem Michael/transesterification reaction of α-hydroxy-1-indanone and α,ß-unsaturated esters. A broad range of spiro(1-indanone-butyrolacones) with contiguous stereocenters have been synthesized with excellent stereoselectivities (up to >20:1 dr, up to >99% ee) under the catalysis of dinuclear zinc complex. Moreover, the reaction can be run on a gram scale without affecting its stereoselectivities. A possible mechanism is proposed.

3.
Org Lett ; 21(7): 2111-2115, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30865463

RESUMO

A new, efficient route for the enantioselective construction of bispirotetrahydrofuran oxindoles is described via the cooperative dinuclear zinc-AzePhenol catalyst. Under mild conditions, a broad range of bispirotetrahydrofuran oxindoles have been synthesized with excellent stereoselectivities through the cascade Michael/hemiketalization/Friedel-Crafts reaction of ß,γ-unsaturated α-ketoamide and 2-hydroxy-1-indanone. The reaction can be performed on a gram scale with low catalyst loading (2 mol %) without impacting its efficiency.

4.
Front Pharmacol ; 7: 255, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27588003

RESUMO

Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (BZP) is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated. For the purpose of investigating the pharmacokinetic profiles, tissue distribution, and plasma protein binding of BZP and Br-NBP, a rapid, sensitive, and specific method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS) has been developed for determination of BZP and Br-NBP in biological samples. The results indicated that BZP and Br-NBP showed a short elimination half-life, and pharmacokinetic profile in rats (3, 6, and 12 mg/kg; i.v.) and beagle dogs (1, 2, and 4 mg/kg; i.v.gtt) were obtained after single dosing of BZP. After multiple dosing of BZP, there was no significant accumulation of BZP and Br-NBP in the plasma of rats and beagle dogs. Following i.v. single dose (6 mg/kg) of BZP to rats, BZP and Br-NBP were distributed rapidly into all tissues examined, with the highest concentrations of BZP and Br-NBP in lung and kidney, respectively. The brain distribution of Br-NBP in middle cerebral artery occlusion (MCAO) rats was more than in normal rats (P < 0.05). The plasma protein binding degree of BZP at three concentrations (8000, 20,000, and 80,000 ng/mL) from rat, beagle dog, and human plasma were 98.1-98.7, 88.9-92.7, and 74.8-83.7% respectively. In conclusion, both BZP and Br-NBP showed short half-life, good dose-linear pharmacokinetic profile, wide tissue distribution, and different degree protein binding to various species plasma. This was the first preclinical pharmacokinetic investigation of BZP and Br-NBP in both rats and beagle dogs, which provided vital guidance for further preclinical research and the subsequent clinical trials.

5.
Chemistry ; 21(34): 11994-8, 2015 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-26177976

RESUMO

A new highly enantioselective domino Michael/hemiketalization reaction of α-hydroxyacetophenone with ß,γ-unsaturated α-keto esters for the synthesis of 2,2,4,5-tetrasubstituted chiral tetrahydrofurans is reported. With 2 mol % intramolecular dinuclear zinc-AzePhenol complex prepared in situ from the reaction of multidentate semi-azacrown ether ligand with ZnEt2 , the corresponding anti-multisubstituted tetrahydrofuran products were obtained in up to 90 % yields, and 98 % enantiomeric excess (ee) at 0 °C for 45 min. Moreover, the products were easily converted to 2,3,5-trisubstituted 2,3-dihydrofurans without any loss in optical activity.

6.
J Mater Chem B ; 3(18): 3677-3680, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32262841

RESUMO

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles with bicyclol (5%) and 3-n-butyl-6-bromophthalid (Br-NBP) (3%) were prepared by an emulsification-solvent evaporation technique. The PLGA nanoparticles were, for the first time, successfully characterized by a laser trapping/confocal Raman spectroscopic technique using only individual PLGA nanoparticles. This technique allowed us to selectively obtain Raman spectra of optically trapped PLGA nanoparticles (∼10 nanoparticles) in solution. The Raman spectra of the PLGA nanoparticles loaded with hydrophobic drugs showed that these drugs were incorporated in the nanoparticles.

7.
J Org Chem ; 79(23): 11690-9, 2014 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-25392948

RESUMO

A highly enantioselective Friedel-Crafts (F-C) alkylation of pyrrole with a wide range of simple nonchelating chalcone derivatives catalyzed by a chiral (Zn2EtL)n (L = (S,S)-1) complex has been developed. The catalyst (Zn2EtL)n complex was prepared in situ by reacting the chiral ligand (S,S)-1 with 2 equiv of diethylzinc. A series of ß-pyrrole-substituted dihydrochalcones were usually formed mostly in excellent yields (up to 99%) and excellent enantioselectivity [up to 99% enantiomeric excess (ee)] by using 15 mol % catalyst loading under mild conditions. The absolute stereochemistry of the products was determined to be the S-configuration by X-ray crystallographic analysis of 13g. Meanwhile, a weak negative nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible mechanism was proposed to explain the origin of the asymmetric induction.

8.
PLoS One ; 9(8): e105617, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25144636

RESUMO

Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC(50)s ranging from 0.03 to 6.92 nM) and HIV-2 (EC(50)s ranging from 0.018 to 0.025 nM). It also showed synergism in combination with six approved anti-HIV drugs on both C8166 and PBMC. In combination assay, the concentrations of azvudine used were 1000 or 500 fold lower than other drugs. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). Although M184V caused 250 fold reduction in susceptibility, azvudine remained active at nanomolar range. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in azvudine treatment. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of azvudine. The present data demonstrates the potential of azvudine as a complementary drug to current anti-HIV drugs. M184I should be the key mutation, however, azvudine still remains active on HIV-1LAI-M184V at nanomolar range.


Assuntos
Fármacos Anti-HIV/farmacologia , Azidas/farmacologia , Desoxicitidina/análogos & derivados , Farmacorresistência Viral , HIV/efeitos dos fármacos , Lamivudina/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Fármacos Anti-HIV/química , Azidas/química , Linhagem Celular , Desoxicitidina/química , Desoxicitidina/farmacologia , Genótipo , HIV/enzimologia , HIV/genética , Transcriptase Reversa do HIV/química , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Ligação Proteica , Inibidores da Transcriptase Reversa/química , Replicação Viral/efeitos dos fármacos
9.
Chemistry ; 20(39): 12394-8, 2014 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-25112517

RESUMO

A new ligand can be easily prepared, and its intramolecular dinuclear zinc complexes act as a high performance catalyst for the asymmetric alternating copolymerization of cyclohexene oxide and CO2 under very mild conditions (1 atm CO2 , room temperature), affording completely alternating polycarbonates with up to 93.8 % enantiomeric excess (ee) and 98 % yield. A high Mn value of 28 600 and a relatively narrow polydispersity (Mw /Mn ratio) of 1.43 were also achieved.

10.
Asian Pac J Cancer Prev ; 15(16): 6829-35, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25169533

RESUMO

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'- deoxy- 2' -ß- fluoro -4'- azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with IC50 values of 0.2µM and 0.097µM, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ß-catenin, the glycogen synthase kinase-3 beta (GSK-3ß), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ß-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-3ß and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/ß-catenin signaling pathway.


Assuntos
Antineoplásicos/farmacologia , Azidas/farmacologia , Desoxicitidina/análogos & derivados , Linfoma não Hodgkin/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Caderinas/biossíntese , Caderinas/genética , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/farmacologia , Quinase 3 da Glicogênio Sintase/biossíntese , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Invasividade Neoplásica/prevenção & controle , RNA Mensageiro/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética , Proteínas Wnt/antagonistas & inibidores , beta Catenina/antagonistas & inibidores , beta Catenina/biossíntese , beta Catenina/genética
11.
J Nat Prod ; 77(2): 397-401, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24499304

RESUMO

Four new stilbene derivatives, polygonumosides A-D (1-4), were isolated from the processed roots of Polygonum multiflorum. Their structures were elucidated by spectroscopic analysis, including 1D and 2D NMR and ECD. Polygonumosides A (1) and B (2), possessing an unprecedented tetracyclic skeleton, were assigned as 2S- and 2R-2-(4-hydroxyphenyl)-9,10,11-trihydroxy-2H-benzo[c]furo[2,3-f]chromen-7(3H)-one-4-O-ß-d-glucopyranosides, respectively, while polygonumosides C (3) and D (4) were assigned as a pair of diastereomeric stilbene glucoside dimers.


Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Glucosídeos/isolamento & purificação , Polygonum/química , Estilbenos/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Glucosídeos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Estilbenos/química
12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(2): 291-6, 2013 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-23591354

RESUMO

OBJECTIVE: To study the influence of HPMC as hydrophilic matrix materials and controlled-layer components on the drug release of sustained-release matrix tablets and bilayer tablets. METHODS: Diltiazem hydrochloride was chosen as the water-soluble model drug to prepare different kinds of matrix tablets and double layer tablets with different formulations, and evaluate how the levels and grades of HPMC affect the drug release in sustained-release tablets and bilayer tablets. RESULTS: HPMC with high viscosity and the amount of 20%-40% could delay the drug release to certain degree, but it was difficult to further slow down the drug release up to 24 h, especially for a water soluble drug. Combining HPMC with 5%-20% of CMC-Na was proven to be an effective way to achieve the 24 h release profile with the water soluble drug. HPMC was also investigated as a component in the double layer tablet as base layer. Drug release was complicated compared with EC as the base layer in the double layer tablet due to the great swelling ability of HPMC. HPMC's larger swilling let it form a big cap to retard the drug release, which could significantly affect the drug release with a large ratio of the base layer to the drug layer; furthermore increasing the quality of 10%-40% of the base layer and the proportion of HPMC could reduce the initial burst release. CONCLUSION: The grade/level of HPMC and combinations with other matrix materials had a big impact on the drug release. HPMC could be used in the base layer of the double tablet to alternate the drug release profile, and reduce the initial burst release of the double-layer matrix tablet, and potentially change the drug mechanism.


Assuntos
Preparações de Ação Retardada/química , Metilcelulose/análogos & derivados , Metilcelulose/química , Composição de Medicamentos , Lactose/análogos & derivados , Lactose/química , Propranolol/química , Comprimidos/química , Tecnologia Farmacêutica/métodos
13.
Eur J Pharmacol ; 702(1-3): 258-63, 2013 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-23415746

RESUMO

α-DDB-DU, 2'-deoxy-3'-(4,4'-dimethoxy-2'-methoxycarbonyl-5,6,5',6'-bis(methylenedioxy)-1,1'-biphenyl-2-carboxyl)uridine, is a novel nucleoside analogue accomplished by linking α-DDB (α-dimenthoxy dicarboxylate biphenyl) and DU (2'-deoxyuridine) via an ester bond. In the current study, the anti-HBV activity and hepatoprotective effect of this compound were investigated both in vitro and in vivo. In the human HBV-transfected liver cell line HepG2.2.15, α-DDB-DU effectively suppressed the secretion of the HBV antigens in a dose-dependent manner, with inhibition rate of 42.31% for HBsAg and 31.52% for HBeAg at 5 µM on day 9. In addition, it could inhibit the viral DNA replication effectively at the concentration of 5 µM, with 81.18% intracellular inhibition and 88.55% extracellular inhibition, respectively, on day 9. In the duck hepatitis B virus (DHBV) infected model, DHBV DNA levels were markedly reduced after treatment with the α-DDB-DU at the dosages of 0.8 mg/kg day, 4 mg/kg day and 20 mg/kg day. The inhibition rate of α-DDB-DU at the dose of 20 mg/kg day reached 93.75% and 89.43%, in duck serum and liver, respectively, on day 10. Furthermore, the levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in both serum and livers were notably reduced on day 10 and histopathological evaluation of the animals' livers indicated significant improvement. In conclusion, α-DDB-DU possesses significant inhibitory activity against HBV replication and ameliorates hepatic pathology significantly.


Assuntos
Antivirais/farmacologia , Benzodioxóis/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Uridina/análogos & derivados , Animais , Benzodioxóis/uso terapêutico , DNA Viral/análise , Patos , Feminino , Células Hep G2 , Hepatite B/tratamento farmacológico , Hepatite B/patologia , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Masculino , Uridina/farmacologia , Uridina/uso terapêutico
14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 44(5): 742-8, 2012 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-23073585

RESUMO

OBJECTIVE: To study the release profiles of Ambroxol hydrochloride in matrix tablets with different fillers and controlled release materials, and investigate the potential impact on different fillers on the matrix tablet's scale-up. METHODS: Ambroxol hydrochloride was chosen as the model drug to make single-layer matrix tablets with different types of hydroxylpropyl methylcellulose as matrix material, and lactose or microcrystalline cellulose as the filler. In vitro dissolution test was used to evaluate the drug release performance of the matrix tablets made. Also ethyl cellulose was used to prepare double-layer matrix tablets to investigate how different kinds of hydroxypropyl methylcellulose (HPMC) and fillers would affect the drug release in double-layer matrix tablets. RESULTS: The drug release rate of single-layer tablets with lactose and HPMC decreased significantly with the increase of the level and viscosity of HPMC. However the release profile only slightly slowed down with the increase of the content and viscosity of HPMC for single-layer matrix tablets of microcrystalline cellulose (MCC). Compared with the single-layer tablets, the level and viscosity of HPMC had less impact on the drug release of the double-layer matrix tablets. CONCLUSION: The matrix tablet with lactose and HPMC has greater flexibility to design formulations with different drug release rate, however the introduction of other process parameters during the scale-up could lead the shifting of the drug release profile from small scale batches. The drug release profiles of matrix tablets with insoluble filler-MCC only change within a small range with the increase of the level and viscosity of HPMC. From the formulation design point of view, it could be necessary to select different type of controlled release polymers to meet the design requirement.


Assuntos
Ambroxol/administração & dosagem , Preparações de Ação Retardada/química , Portadores de Fármacos , Expectorantes/administração & dosagem , Química Farmacêutica , Excipientes/química , Lactose/química , Metilcelulose/análogos & derivados , Metilcelulose/química , Comprimidos
15.
Pest Manag Sci ; 67(9): 1141-6, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21452169

RESUMO

BACKGROUND: As previously reported, methyl (E)-2-[2-(2-phenylamino-6-trifluoromethylpyrimidin-4-yloxymethyl)phenyl]-3-methoxyacrylate has proven to be a new lead with highly acaricidal activity. Following on from this, in an effort to discover new strobilurin analogues with improved activity, a series of substituted pyrimidines were synthesised and bioassayed. RESULTS: All compounds were characterised by (1) H NMR, IR, MS and elemental analysis. Preliminary bioassays demonstrated that some of the title compounds exhibited notable control of Tetranychus cinnabarinus (Boisd.) at 1.25 mg L(-1) . The relationship between structure and acaricidal activity is discussed. CONCLUSION: Two compounds of particular interest, 6j (SYP-10913) and 6k (SYP-11277), exhibited potent acaricidal activity. The acaricidal potencies of these analogues are higher than that of fluacrypyrim in greenhouse applications, and are comparable with those of commercial acaricides such as spirodiclofen and propargite in field trials.


Assuntos
Acaricidas/toxicidade , Ácaros/efeitos dos fármacos , Pirimidinas/toxicidade , Acaricidas/síntese química , Acaricidas/química , Animais , Descoberta de Drogas , Fabaceae/parasitologia , Feminino , Masculino , Estrutura Molecular , Doenças das Plantas/parasitologia , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
16.
Brain Res ; 1358: 239-47, 2010 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-20732309

RESUMO

Oxidative stress, an imbalance toward the prooxidant side of the prooxidant/antioxidant homeostasis, occurs in several brain neurodegenerative disorders. The protective effect of 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP), a derivative compound of l-3-n-butylphthalide (NBP), on the hydrogen peroxide(H(2)O(2))- induced oxidative damage was investigated in PC12 cells. Following exposure of the cells to H(2)O(2), there was a significant reduction in cell survival,activities of glutathione peroxidase (GSH-px) and mitochondria membrane potential(MMP), in contrast, the increased levels in the leakage of lactate dehydrogenase (LDH), malondialdehyde (MDA) contents, nitric oxide (NO) productions, intracellular reactive oxygen species (ROS), intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as cell apoptosis were observed. However, pretreatment of cells with Br-NBP prior to H(2)O(2) exposure attenuated all the changes mentioned above in a concentration-dependent manner except no effect on activities of GSH-px. Br-NBP exhibited the protective effect against H(2)O(2)-induced cytotoxicity in PC12 cells, suggesting that the compound may be a potential therapeutic agent for diseases induced by oxidative damage.


Assuntos
Benzofuranos/farmacologia , Peróxido de Hidrogênio/toxicidade , Fármacos Neuroprotetores/farmacologia , Oxidantes/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Interações Medicamentosas , Glutationa Peroxidase/metabolismo , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células PC12/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo
17.
Pest Manag Sci ; 66(11): 1208-14, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20681007

RESUMO

BACKGROUND: The intermediate derivatisation method based on bioisosteric replacement led to the discovery of the lead strobilurin compound 5a. To produce new strobilurin analogues with improved activity, a series of substituted pyrimidines were synthesised and bioassayed. RESULTS: The compounds were identified by (1)H NMR, IR, MS and elemental analysis. The highly active compound 5 g was studied by X-ray diffraction. Preliminary bioassays demonstrated that some of the title compounds exhibited excellent acaricidal activity against Tetranychus cinnabarinus (Boisd.) at 10 mg L(-1). The relationship between structure and acaricidal activity is reported. CONCLUSION: The present work demonstrates that strobilurin derivatives containing pyrimidine moieties can be used as possible lead compounds for developing novel acaricides.


Assuntos
Acaricidas/química , Metacrilatos/química , Acaricidas/síntese química , Animais , Chumbo/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Controle de Pragas , Pirimidinas/química , Tetranychidae
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(1): 35-7, 2010 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-20302075

RESUMO

Poly(propylene fumarate) (PPF) is one kind of linear biodegradable polyester and the unsaturated double bonds along its main chain can be crosslinked with other olefinic monomers to form three-dimensional networks, and the networks can support tissues. In the present paper, firstly, the intermediate oligomer-bis (2-hydroxypropyl) fumarate (PFP) was synthesized, and then the unsaturated linear polyester PPF was synthesized with the oligomer PFP through melting condensation process. Additionally, on the base of the process, the oligomer bis(2-hydroxypropyl) sebacate (PSP) was synthesized by similar method and then a kind of new copolymer named poly(propylene fumarate-co-propylene sebacate) [P(PF-co-PS)] that comprised bis(2-hydroxypropyl) sebacate segments was synthesized with PFP and PSP by melting condensation. During the synthesis process, the structures of bis(2-hdroxypropyl) fumarate, bis(2-hydroxypropyl) sebacate, PPF and P(PF-co-PS) were characterized by FTIR The results shows that with the polymerization going along, oligomer bis (2-hydroxypropyl) fumarate and bis(2-hydroxypropyl) sebacate converted to PPF or P(PF-co-PS) gradually.


Assuntos
Materiais Biocompatíveis/síntese química , Fumaratos/síntese química , Polipropilenos/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier , Materiais Biocompatíveis/química , Fumaratos/química , Polipropilenos/química
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(1): 87-9, 2010 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-20302088

RESUMO

dl-NBP is a potentially beneficial and promising drug for treatment of ischemic stroke with multiple actions that affect different pathophysiologic processes, such as improving microcirculation, decreasing brain infarct volume, regulating energy metabolism, and especially inhibiting platelet aggregation and reducing thrombus formation. However, NBP is limited to use in the clinic by other side effects, such as elevated aminotransferase, abnormal liver function and digestive response. Some derivates of NBP were synthesized with the halides (F, Cl and Br) on the 6-position, and their IR and Raman spectra were measured. They proved the complemental information for deducing their structure. By comparing the spectra of the NBP, the band of disubstituted benzene disappeared in the derivatives, and the band of trisubstituted benzenes were observed. The stretching vibrational band of C--H was detected in the Raman spectra, but was not observed in IR. In the low frequency region, the deformation vibration band of --C--C--C--C was also observed in the Raman spectra.


Assuntos
Benzofuranos/química , Espectrofotometria Infravermelho , Análise Espectral Raman
20.
Eur J Med Chem ; 45(5): 1941-6, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20133025

RESUMO

A series of n-butylphthalide derivatives were designed and synthesized. The in vitro activities of these compounds were evaluated by a resting tension of isolated rat thoracic aorta ring assay. Compounds 4g and 4i were found to be more active than n-butylphthalide.


Assuntos
Aorta Torácica/efeitos dos fármacos , Benzofuranos/síntese química , Benzofuranos/farmacologia , Vasodilatadores/síntese química , Vasodilatadores/farmacologia , Animais , Aorta Torácica/metabolismo , Benzofuranos/química , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Camundongos , Estrutura Molecular , Ratos , Estereoisomerismo , Vasodilatadores/química
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