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1.
Pest Manag Sci ; 71(3): 404-14, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24777582

RESUMO

BACKGROUND: Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin analogues with broad spectrum and high activity, a series of novel oxime ether strobilurin derivatives containing substituted benzofurans in the side chain were synthesised and bioassayed. RESULTS: The synthesised compounds were characterised by (1) H NMR, (13) C NMR, MS and HRMS. Bioassays demonstrated that most target compounds possessed good or excellent fungicidal activities, especially against Erysiphe graminis and Pyricularia oryzae. Furthermore, methyl 3-methoxypropenoate oxime ethers exhibited remarkably higher activities against E. graminis, Colletotrichum lagenarium and Puccinia sorghi Schw. Notably, (E,E)-methyl 3-methoxy-2-{2-[({[5-fluoro-1-(benzofuran-2-yl)ethylidene]amino}oxy)methyl]phenyl}propenoate (BSF2) and (E,E)-methyl 3-methoxy-2-{2-[({[5-chloro-1-(benzofuran-2-yl)ethylidene]amino}oxy)methyl]phenyl}propenoate (BSF3) were identified as the most promising candidates for further study. CONCLUSION: The present work demonstrates that oxime ether strobilurin derivatives containing benzofurans can be used as possible lead compounds for developing novel fungicides.


Assuntos
Fungos/efeitos dos fármacos , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Ácidos Graxos Insaturados/síntese química , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/farmacologia , Fungicidas Industriais/farmacologia , Espectroscopia de Ressonância Magnética , Metacrilatos/síntese química , Metacrilatos/química , Metacrilatos/farmacologia , Oximas/síntese química , Oximas/química , Oximas/farmacologia , Relação Estrutura-Atividade
2.
Bioorg Med Chem Lett ; 24(9): 2173-6, 2014 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24717155

RESUMO

Twenty-one novel benzothiophene-substituted oxime ether strobilurins, which employed a benzothiophene group to stabilise the E-styryl group in Enoxastrobin (an unsaturated oxime strobilurin fungicide developed by Shenyang Research Institute of Chemical Industry, China) were designed and synthesised. The biological assay indicated that most compounds exhibited good or excellent fungicidal activities, especially against Colletotrichum lagenarium and Puccinia sorghi Schw. In addition, methyl 3-methoxypropenoate oxime ethers and N-methoxy-carbamic acid methyl esters exhibited good in vivo fungicidal activities against Erysiphe graminis, Colletotrichum lagenarium and Puccinia sorghi Schw. under the tested concentrations. Notably, (E,E)-methyl 3-methoxy-2-(2-((((6-chloro-1-(1H-benzo[b]thien-2-yl)ethylidene)amino)oxy)methyl)phenyl)propenoate (5E) exhibited more potent in vivo fungicidal activities against nearly all of the tested fungi at a concentration of 0.39 mg/L compared to Enoxastrobin.


Assuntos
Fungos/efeitos dos fármacos , Fungicidas Industriais/química , Fungicidas Industriais/toxicidade , Tiofenos/química , Tiofenos/toxicidade , Ácidos Graxos Insaturados/síntese química , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/toxicidade , Fungicidas Industriais/síntese química , Metacrilatos/síntese química , Metacrilatos/química , Metacrilatos/toxicidade , Oximas/síntese química , Oximas/química , Oximas/toxicidade , Estrobilurinas , Tiofenos/síntese química
3.
Shanghai Kou Qiang Yi Xue ; 22(6): 671-5, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24469131

RESUMO

PURPOSE: To investigate the relationship between mental health status and catecholamines level in oral squamous cell carcinoma patients. METHODS: Forty patients with oral squamous carcinoma (OSCC) who were diagnosed in West China School of Stomatology between Dec. 2011 and Aug. 2012, were assessed with symptom checklist-90 (the 5-grade scoring of 0 to 4 points was used) independently according to their actual conditions. Blood sample was taken on the second admission day and fresh tumor tissue with the weight of 0.5 g was obtained. A method was developed for determination of catecholamine and glucocorticoid in serum using liquid chromatography-tandem mass spectrometry (HPLC-MS-MS). SPSS19.0 software package was used for statistical analysis. RESULTS: Forty patients were included in the study. Compared with the scores of SCL-90 in national norms, the scores were all higher in oral squamous carcinoma patients except the interpersonal relationship. Epinephrine(E) and norepinephrine(NE) in serum was (70.27±34.50) pg/mL and (316.73±109.22) pg/mL, respectively. E and NE in tumor tissues was (6.66±3.58) pg/mg and (12.67±5.27) pg/mg respectively. As the concentrations of NE and E from circulating serum increasing, the stage and grade of oral squamous carcinoma were promoted. CONCLUSIONS: Psychiatric factors have an important impact on OSCC patients. The increased level of catecholamines is closely related to clinical stage and grade of OSCC. Supported by National Natural Science Foundation of China (81172578) and Natural University Students Innovation Training Program (201210610096).


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Catecolaminas , Nível de Saúde , Humanos
4.
Int J Mol Sci ; 13(6): 6849-62, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22837667

RESUMO

In the present study, the 26-residue amphipathic α-helical peptide A12L/A20L (Ac-KWKSFLKTFKSLKKTVLHTLLKAISS-amide) with strong anticancer activity and specificity was used as the framework to study the effects of helicity of α-helical anticancer peptides on biological activities. Helicity was systematically modulated by introducing d-amino acids to replace the original l-amino acids on the non-polar face or the polar face of the helix. Peptide helicity was measured by circular dichroism spectroscopy and was demonstrated to correlate with peptide hydrophobicity and the number of d-amino acid substitutions. Biological studies showed that strong hemolytic activity of peptides generally correlated with high hydrophobicity and helicity. Lower helicity caused the decrease of anti-HeLa activity of peptides. By introducing d-amino acids to replace the original l-amino acids on the non-polar face or the polar face of the helix, we improved the therapeutic index of A12L/A20L against HeLa cells by 9-fold and 22-fold, respectively. These results show that the helicity of anticancer peptides plays a crucial role for biological activities. This specific rational approach of peptide design could be a powerful method to improve the specificity of anticancer peptides as promising therapeutics in clinical practices.


Assuntos
Antineoplásicos/química , Química Farmacêutica/métodos , Peptídeos/química , Estrutura Secundária de Proteína , Sequência de Aminoácidos , Aminoácidos/química , Peptídeos Catiônicos Antimicrobianos/química , Cátions , Dicroísmo Circular , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Eritrócitos/efeitos dos fármacos , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Concentração Inibidora 50 , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos
5.
Chem Biol Drug Des ; 78(5): 835-43, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21801309

RESUMO

Lack of vaccines for HCV and HIV makes the antiviral drug development urgently needed. The recently identified HCV NS5A-derived virucidal peptide (C5A) demonstrated a wide spectrum of activities against viruses. In this study, the C5A sequence SWLRDIWDWICEVLSDFK was utilized as the framework to study the effect of the modulation of peptide helicity and hydrophobicity on its anti-HCV and anti-HIV activities. Peptide helicity and hydrophobicity were altered by substitutions of varying amino acids on the non-polar face of C5A. Peptide hydrophobicity has been proved to play a crucial role in peptide anti-HCV or anti-HIV activities. Peptide helicity was relatively independent with antiviral activity. However, peptide analogs with dimerized structure in an aqueous medium while maintaining the ability to be induced into a more helical structure in a hydrophobic environment may tend to show comparable or improved antiviral activity and specificity to C5A. By modulating peptide helicity and hydrophobicity, we improved the specificity of C5A against HCV and HIV by 23- and 69-fold, respectively, in terms of the ratio of hemolytic activity to antiviral activity. We demonstrated that obtained by de novo design approach, peptide I6L/I10L/V13L may be a promising candidate as a new anti-HCV and anti-HIV therapeutic.


Assuntos
Fármacos Anti-HIV/química , Antivirais/química , Desenho de Drogas , Peptídeos/química , Sequência de Aminoácidos , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Eritrócitos/efeitos dos fármacos , HIV/efeitos dos fármacos , Hemólise , Hepacivirus/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/farmacologia , Estrutura Secundária de Proteína , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
6.
Mol Cancer Ther ; 10(3): 416-26, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21252288

RESUMO

In the present study, the hydrophobicity of a 26-residue α-helical peptide (peptide P) was altered to study the effects of peptide hydrophobicity on the mechanism of action of cationic anticancer peptides. Hydrophobicity of the nonpolar face of the peptides was shown to correlate with peptide helicity. The self-association ability of peptides in aqueous environment, determined by the reversed-phase high performance liquid chromatography temperature profiling, showed strong influence on anticancer activity. The peptide analogues with greater hydrophobicity showed stronger anticancer activity determined by IC(50) values with a necrotic-like membrane disruption mechanism. Peptide analogues exhibited high specificity against cancer cells and much higher anticancer activity than widely-used anticancer chemical drugs. The mechanism of action of anticancer peptides was also investigated. The hydrophobicity of peptides plays a crucial role in the mechanism of action against cancer cells, which could present a way, using a de novo design approach, to create anticancer peptides as potential therapeutics in clinical practices.


Assuntos
Antineoplásicos/farmacologia , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Membranas/efeitos dos fármacos , Peptídeos/farmacologia , Linhagem Celular Tumoral , Cromatografia de Fase Reversa , Dicroísmo Circular , Humanos , Microscopia Confocal , Microscopia Eletrônica de Varredura , Relação Estrutura-Atividade
7.
Prep Biochem Biotechnol ; 38(2): 158-71, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18320467

RESUMO

The protease-catalyzed, kinetically controlled synthesis of a precursor dipeptide of thymopentin(TP-5), Z-Arg-Lys-NH2 in organic solvents was studied. Z-Arg-OMe was used as the acyl donor and Lys-NH2 was used as the nucleophile. An industrial alkaline protease alcalase and trypsin were used to catalyze the synthesis of the target dipeptide in water-organic cosolvent systems. The conditions of the synthesis reaction were optimized by examining the effects of several factors, including organic solvents, water content, temperature, pH, and reaction time on the yield of Z-Arg-Lys-NH2. The optimum conditions using alcalase as the catalyst are pH 10.0, 35 degrees C, in acetonitrile/DMF/Na2CO3-NaHCO3 buffer system (80:10:10, V/V), 6 h, with the dipeptide yield of 71.1%. Compared with alcalase, the optimum conditions for trypsin are pH 8.0, 35 degrees C, in ethanol/Tris-HCl buffer system (80:20, V/V), 4 h, with the dipeptide yield of 76.1%.


Assuntos
Amidoidrolases/química , Dipeptídeos/síntese química , Compostos Orgânicos/química , Precursores de Proteínas/síntese química , Solventes/química , Timopentina/química , Tripsina/química
8.
Biotechnol Appl Biochem ; 51(Pt 3): 119-27, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18248327

RESUMO

In the present study, a precursor tetrapeptide Bz-RGDS-NH2 (N-benzoylarginylglycylaspartylserinamide) of cell-adhesion peptide RGDS (arginylglycylaspartylserine) was synthesized by a novel route. First of all, the precursor tripeptide GDS-NH2 (glycylaspartylserinamide) was synthesized by a chemical method only using aspartic acid and serine at gram scale in four steps. The linkage of the fourth amino acid Bz-Arg-OEt (N-benzoyl-L-arginine ethyl ester) to GDS-NH2 was completed by an enzymatic method under kinetic control in water-miscible organic media. An industrial alkaline protease, Alcalase, with a wide substrate specificity, was used as the catalyst. The effects of organic solvents, pH value, reaction temperature, water content and molar ratio of substrates on the yield of Bz-RGDS-NH2 synthesis were examined. The optimum reaction conditions were found to be pH 10.0, 35 degrees C, 8 h, in an acetonitrile/(Na2CO3/NaHCO3) buffer system (93:7, v/v) with a maximal yield of 65.2%. We found that secondary hydrolysis of the peptide product did not take place in these water-miscible organic solvents.


Assuntos
Oligopeptídeos/síntese química , Oligopeptídeos/imunologia , Oligopeptídeos/metabolismo , Subtilisinas/metabolismo , Catálise , Adesão Celular , Concentração de Íons de Hidrogênio , Cinética , Oligopeptídeos/química , Oligopeptídeos/isolamento & purificação , Solubilidade , Solventes/química , Especificidade por Substrato , Temperatura Ambiente , Fatores de Tempo , Água/química
9.
Prep Biochem Biotechnol ; 36(3): 243-52, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16707335

RESUMO

A new route was employed to synthesize RGD. First, Gly-Asp dipeptide was synthesized by a novel chemical method in two steps, including chloroacetylation of L-aspartic acid and ammonolysis of chloroacetyl L-aspartic acid. Second, Nalpha-Z- L-Arginine was reacted with Gly-Asp to synthesize RGD by the N-carboxyanhydride method. Less protected amino acids were used in this synthesis. This method possessed advantages of low cost, simplicity, and rapidity with a reasonable yield of 62% calculated from arginine. In addition, compared with the above method, a conventional solid phase method was also used to synthesize RGD, the yield was 75% calculated from the first amino acid anchored to resin.


Assuntos
Oligopeptídeos/síntese química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Oligopeptídeos/química
10.
J Biotechnol ; 125(3): 311-8, 2006 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-16621088

RESUMO

The tetrapeptide Bz-Arg-Gly-Asp-Ser-NH(2) (Bz-RGDS-NH(2)) was successfully synthesized by a combination of chemical and enzymatic methods in this study. Firstly, the precursor tripeptide Gly-Asp-Ser-NH(2) (GDS-NH(2)) was synthesized by a novel chemical method in four steps including chloroacetylation of l-aspartic acid, synthesis of chloroacetyl l-aspartic acid anhydride, the synthesis of ClCH(2)COAsp-SerOMe and ammonolysis of ClCH(2)COAsp-SerOMe. Secondly, lipase (PPL) was used to catalyze the formation of Bz-RGDS-NH(2) in aqueous water-miscible organic cosolvent systems using Bz-Arg-OEt as the acyl donor and GDS-NH(2) as the nucleophile. The optimum conditions were Bz-Arg-OEt 50 mM; GDS-NH(2) 400 mM; 10 degrees C, 0.1M phosphate buffer, pH 7.5; 60% DMF or 58% DMSO, PPL: 10 mg ml(-1) with the maximum yields of the tetrapeptide of 73.6% for DMF and 70.4% for DMSO, respectively. The secondary hydrolysis of the tetrapeptide product did not take place due to the absence of amidase activity of lipase.


Assuntos
Química Inorgânica/métodos , Lipase/farmacologia , Oligopeptídeos/síntese química , Catálise , Concentração de Íons de Hidrogênio , Concentração Osmolar , Solventes/farmacologia , Temperatura Ambiente , Fatores de Tempo , Água/farmacologia
11.
Biotechnol Appl Biochem ; 44(Pt 2): 73-80, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16420189

RESUMO

Synthesis of Bz-Arg-Gly-NH(2) (N-benzoylargininylglycinamide) [a precursor dipeptide of RGDS (Arg-Gly-Asp-Ser)] catalysed by protease in water/organic co-solvent systems was studied. Starting substrates were N-benzoyl-L-arginine ethyl ester hydrochloride (acyl donor) and glycinamide (nucleophile). Acetonitrile was selected as the organic solvent. Alcalase, an industrial alkaline protease, was applied to the synthesis of the target dipeptide. The conditions of the synthesis reaction were optimized by examining the effects of several factors, including water content, temperature, pH, molar ratio of the substrates and reaction time, on the yield of Bz-Arg-Gly-NH(2). The optimum conditions were established to be pH 10.0, 45 degrees C, in acetonitrile/0.1 M Na(2)CO(3)/NaHCO(3) buffer system (90:10, v/v) for 1 h with a dipeptide yield of 82.9%.


Assuntos
Dipeptídeos/síntese química , Oligopeptídeos/síntese química , Compostos Orgânicos/química , Subtilisinas/química , Catálise , Temperatura Alta , Concentração de Íons de Hidrogênio , Cinética , Solubilidade , Solventes/química , Água/química
12.
Prep Biochem Biotechnol ; 36(1): 93-105, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16428141

RESUMO

The protease-catalyzed, kinetically controlled synthesis of a precursor dipeptide of RGDS, Z-Asp-Ser-NH2 in organic solvents was studied. Alcalase, an industrial alkaline protease, was used to catalyze the synthesis of the target dipeptide in water-organic cosolvents systems with Z-Asp-OMe as the acyl donor and Ser-NH2 as the nucleophile. Acetonitrile was selected as the organic solvent from acetonitrile, ethanol, methanol, DMF, DMSO, ethyl acetate, 2-methyl-2-propanol, and chloroform tested under the experimental conditions. The conditions of the synthesis reaction were optimized by examining the effects of several factors, including water content, temperature, pH, and reaction time on the Z-Asp-Ser-NH2 yields. The optimum conditions are pH 10.0, 35 degrees C, in acetonitrile/Na2CO3-NaHCO3 buffer system (85:15, v/v), 6 h, with a dipeptide yield of 75.5%.


Assuntos
Dipeptídeos/biossíntese , Oligopeptídeos/biossíntese , Solventes/química , Subtilisinas/metabolismo , Acetonitrilos/química , Ácido Aspártico/análogos & derivados , Ácido Aspártico/síntese química , Ácido Aspártico/metabolismo , Bacillus/enzimologia , Catálise , Cromatografia em Gel , Dextranos/química , Dipeptídeos/isolamento & purificação , Concentração de Íons de Hidrogênio , Cinética , Compostos Orgânicos/química , Serina/análogos & derivados , Serina/síntese química , Serina/metabolismo , Subtilisinas/química , Temperatura Ambiente , Água/química
13.
J Biotechnol ; 116(1): 51-9, 2005 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-15652429

RESUMO

The tripeptide BzArgGlyAsp(NH(2))(2) was synthesized by a combination of chemical and enzymatic methods in this study. First of all, GlyAsp(NH(2))(2) was synthesized by a novel chemical method in three steps including chloroacetylation of L-aspartic acid, esterification of chloroacetyl L-aspartic acid and ammonolysis of chloroacetyl L-aspartic acid diethyl ester. Secondly, kinetically controlled synthesis of BzArgGlyAsp(NH(2))(2) catalyzed by trypsin in organic solvent was conducted. The optimum conditions are pH 8.0, 30 degrees C in ethanol/Tris-HCl buffer system (85:15, v/v) for 80 min in the maximum yield of 74.4%.


Assuntos
Amidas/química , Oligopeptídeos/química , Compostos Orgânicos/química , Solventes/química , Esterificação
14.
Prep Biochem Biotechnol ; 34(1): 45-56, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15046296

RESUMO

Trypsin-catalyzed, kinetically controlled synthesis of a precursor, dipeptide of thymopentin (TP-5), Bz-Arg-Lys-OH (or-OEt) in organic solvents was studied. Bz-Arg-OEt was used as the acyl donor and Lys-OH and Lys-OEt were used as the nucleophiles. Ethanol was selected as the organic solvent from ethanol, methanol, acetonitrile, and ethyl acetate tested under the experimental conditions. As expected, Lys-OEt is not a suitable nucleophile in trypsin-catalyzed reaction, due to its competition with the protective Arg-OEt as acyl donor for the active site of trypsin, while Lys-OH does not have this problem. The optimal reaction condition for the synthesis of Bz-Arg-Lys-OH was set up as 20% Tris-HCl buffer, pH 8.0, 35 degrees C for 6 h with the yield of 52.5%, or for 18-24 h with the yield of about 60%.


Assuntos
Aminoácidos/química , Dipeptídeos/síntese química , Timopentina/síntese química , Tripsina/química , Catálise , Cromatografia Líquida de Alta Pressão , Precursores de Proteínas/síntese química , Solventes
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