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1.
Phytochem Anal ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31359561

RESUMO

INTRODUCTION: Essential oils of Cymbopogon nardus and C. winterianus have fungicidal, bactericidal, and insect repellent activities. In addition, they are components of fragrances, cosmetics, and household products. The growing demand for essential oils has intensified adulteration practices of such products. OBJECTIVES: To evaluate the authenticity and quality of citronella commercial essential oils based on chemical composition [by gas chromatography mass spectrometry (GC-MS)] and the contents of its major constituents [by 1 H-NMR, and gas chromatography with a flame ionisation detector using internal standardisation (GC-IS)]. MATERIALS AND METHODS: The chemical composition of essential oil was determined by GC-MS. Major components were quantified by 1 H-NMR and the results compared to those obtained by GC-IS. RESULTS: The adulteration of oils was verified by GC and 1 H-NMR. In the pure oils, the results obtained by 1 H-NMR were similar to those obtained by GC-IS for most of the oils. However, in adulterated oils, signal overlap prevented the quantification of citronellol and geraniol by NMR. Importantly, due to dilution with dipropylene glycol it was not possible to quantify citronellal using 1 H-NMR. However, for both pure and adulterated oils, GC-IS method proved successful in quantifying notable constituents. CONCLUSION: All the methods used proved efficient in detecting adulteration. However, whilst GC-IS provided quantification of constituents of interest, both in pure and adulterated oils, their quantification by NMR was only possible in non-adulterated samples. None of the oils evaluated presented a composition within the threshold established by British Pharmacopoeia quality standards.

2.
Eur J Med Chem ; 168: 436-446, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30840925

RESUMO

In this study, a series of C-28 amides derivatives of hederagenin with or without the presence of an acetyl group at positions 3 and 23 in ring A, were synthetized aiming to develop potent cytotoxic agents. Their structures were confirmed by MS, IR, 1H NMR and 13C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using a panel of six human cancer cell lines. The majority of the amide derivatives were cytotoxic for a variety of human tumor cell lines. In general, the hydroxylated derivatives (1a-1d; EC50 in the range 1.2-22.5 µM) were less active than the acetylated derivatives (2a-2n; EC50 in the range 0.4-9.0 µM). Hydroxylated derivative bearing pyrrolidinyl substituent 1c, was the most active for HT29 human line cells (EC50 = 1.2 µM), however their acetylated derivative 2c was the most potent and selective against A2780, FaDu, SW1736 cells, showing EC50 values between 0.4 and 1.7 µM and SI between 5.6 and 24. Staining experiments combined with fluorescence microscopy indicate that the cell membrane became permeable, and finally a process of secondary necrosis was observed. In addition, the docking results showed that acetylated compounds display more affinity to HER2 than to USP7, indicating that HER2 is a most probable receptor, both proteins found in tumor cell line A2780.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Ácido Oleanólico/análogos & derivados , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Microscopia de Fluorescência , Simulação de Acoplamento Molecular , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Relação Estrutura-Atividade
3.
Eur J Oral Sci ; 126(3): 214-221, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29517121

RESUMO

This study evaluated the inhibitory effects of lactams on Streptococcus mutans, Enterococcus faecalis, and Candida glabrata multispecies biofilm formation. γ-Alkylidene-γ-lactams 1, 2, and 3 [solubilized in 3.5% dimethyl sulfoxide (DMSO)] were tested. Glass coverslips were conditioned with either the lactams or 3.5% DMSO (control) for 1 h, inoculated with microbial cultures, and incubated for 48 h. To assess the effect of the lactams on biofilm formation, the following parameters were determined: the biofilm biomass (by both crystal violet staining and protein determination); the amount of insoluble polysaccharides of the extracellular matrix; and the number of viable and total cells [by both colony-forming unit counting and quantitative real-time PCR (qPCR)]. Data were analysed using one-way anova and post-hoc Tukey tests. Lactams 1, 2, and 3 promoted a statistically significant reduction in the amount of biofilm biomass, but only lactam 3 resulted in a statistically significant reduction in the number of attached viable E. faecalis. Both total protein content and the amount of extracellular polysaccharides decreased significantly. The effects of γ-alkylidene-γ-lactams 1, 2, and 3 on the inhibition of multispecies biofilm formation were evident by their ability to reduce the amount of protein and extracellular polysaccharides.

4.
J Agric Food Chem ; 65(51): 11304-11311, 2017 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-29191002

RESUMO

Abenquines are natural N-acetylaminobenzoquinones bearing amino acid residues, which act as weak inhibitors of the photosynthetic electron transport chain. Aiming to exploit the abenquine scaffold as a model for the synthesis of new herbicides targeting photosynthesis, 14 new analogues were prepared by replacing the amino acid residue with benzylamines and the acetyl with different acyl groups. The synthesis was accomplished in three steps with a 68-95% overall yield from readily available 2,5-dimethoxyaniline, acyl chlorides, and benzyl amines. Key steps include (i) acylation of the aniline, (ii) oxidation, and (iii) oxidative addition of the benzylamino moiety. The compounds were assayed for their activity as Hill inhibitors, under basal, uncoupled, or phosphorylating conditions, or excluding photosystem I. Four analogues showed high effectiveness (IC50 = 0.1-0.4 µM), comparable with the commercial herbicide diuron (IC50 = 0.3 µM). The data suggest that this class of compounds interfere at the reducing side of photosystem II, having protein D1 as the most probable target. Molecular docking studies with the plastoquinone binding site of Spinacia oleracea further strengthened this proposal.


Assuntos
Benzoquinonas/farmacologia , Transporte de Elétrons/efeitos dos fármacos , Herbicidas/farmacologia , Fotossíntese/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/metabolismo , Spinacia oleracea/metabolismo , Benzoquinonas/química , Cloroplastos/efeitos dos fármacos , Cloroplastos/metabolismo , Herbicidas/química , Simulação de Acoplamento Molecular , Spinacia oleracea/efeitos dos fármacos
5.
Eur J Med Chem ; 140: 624-635, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29024910

RESUMO

Aiming to obtain new potent leishmanicidal and cytotoxic compounds from natural sources, the triterpene hederagenin was converted into several new 1,2,3-triazolyl derivatives tethered at C-23 and C-28. For this work hederagenin was isolated from fruits of Sapindus saponaria and reacted with propargyl bromide to afford as a major product bis-propargylic derivative 1 in 74%. Submitting this compound to Huisgen 1,3-dipolar cycloaddition reactions with several azides afforded the derivatives 2-19 with yields in the range of 40-87%. All compounds have been screened for in vitro cytotoxic activity in a panel of five human cancer cell lines by a SRB assay. The bioassays showed that compound 19 was the most cytotoxic against all human cancer cell lines with EC50 = 7.4-12.1 µM. Moreover, leishmanicidal activity was evaluated through the in vitro effect in the growth of Leishmania infantum, and derivatives 1, 2, 5 and 17 were highly effective preventing proliferation of intracellular amastigote forms of L. infantum (IC50 = 28.8, 25.9, 5.6 and 7.4 µM, respectively). All these compounds showed a higher selectivity index and low toxicity against two strains of kidney BGM and liver HepG2 cells. Compound 5 has higher selectivity (1780 times) in comparison with the commercial antimony drug and is around 8 times more selective than the most active compound previously reported hederagenin derivative. Such high activity associated with low toxicities make the new bis-traiazolyl derivatives promising candidates for the treatment of leishmaniasis. In addition, hederagenin and some derivatives (2, 5 and 17) showed interaction in the binding site of the enzyme CYP51Li.


Assuntos
Antiprotozoários/farmacologia , Ácido Oleanólico/análogos & derivados , Triazóis/química , Animais , Antiprotozoários/uso terapêutico , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Células Cultivadas , Cães , Células Hep G2 , Humanos , Leishmaniose/tratamento farmacológico , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Espectroscopia de Prótons por Ressonância Magnética
6.
J Nat Prod ; 80(7): 2166-2169, 2017 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-28636395

RESUMO

The first synthesis of enhygrolide A, a scarce γ-alkylidenebutenolide antibiotic of the obligate marine myxobacterium Enhygromyxa salina, was achieved in five steps and 54% overall yield from tetronic acid. Key steps include (i) organocatalytic reductive alkylation, (ii) iron-catalyzed sp2-sp3 cross-coupling, and (iii) vinylogous aldol condensation. Aside from its brevity and reliance on environmentally sustainable processes, the synthesis demonstrates the serviceability of butenolide pivalates in cross-coupling reactions.


Assuntos
4-Butirolactona/análogos & derivados , Antibacterianos/síntese química , Compostos de Benzilideno/síntese química , Myxococcales/química , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Aldeídos/química , Alquilação , Antibacterianos/química , Antibacterianos/farmacologia , Compostos de Benzilideno/química , Compostos de Benzilideno/farmacologia , Catálise , Biologia Marinha , Estrutura Molecular , Estereoisomerismo
7.
Bioorg Med Chem Lett ; 27(5): 1141-1144, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28169163

RESUMO

In this study, we explore the cytotoxic activity of four natural abenquines (2a-d) and fourteen synthetic analogues (2e-j and 3a-h) against a panel of six human cancer cell lines using a SRB assay. It was found that most of the compounds revealed higher levels of cytotoxic activities than naturally occurring abenquines. The analogues carrying ethylpyrrolidinyl and ethylpyrimidinyl with either an acetyl group (2h-i) or a benzoyl group (3f-g), were the most potent against all human cancer cell lines and displayed EC50 between a range of 0.6-3.4µM. Notably, of the compounds tested, compound 2i proved the most cytotoxic against both ovarian (A2780) and breast (MCF7) cells, showing EC50=0.6 and 0.8µM respectively. Likewise, the analogues 2i, 3f and 3g showed strong activity against cell HT29 with EC50=0.9µM for these compounds.


Assuntos
Antineoplásicos/farmacologia , Quinonas/farmacologia , Células 3T3 , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Quinonas/química
8.
Bol. latinoam. Caribe plantas med. aromát ; 15(6): 364-372, nov. 2016. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-907553

RESUMO

The chemical composition of the oil extracted from the seeds of Sapindus saponaria L., (Sapindaceae), was investigated. Cyanolipids constituted 5 percent hexane extract of the seeds, whereas triacylglycerols (TAG) accounted for 90 percent. The oil contains type III cyanolipids (CL) 1-cyano-2-hydroxymethylprop-1-en-3-ol-diesters. Structural investigation of the oil components was accomplished by chemical, chromatographic (TLC, CC, GC-MS), and spectroscopic (IR, NMR) means. GC-MS analysis showed that fatty acids were dominant in the CL components of the oil from S. saponaria L., with cis-11-eicosenoic acid, cis-11-octadecenoic acid and eicosanoic acid as the only esterified fatty acyl chains respectively. This being the first report of this kind of natural products (CL), located in the seeds of this plant.


La composición química del aceite de las semillas de Sapindus saponaria L., (Sapindaceae), fue investigada. Cianolípidos (CL) constituyen el 5 por ciento del extracto hexanico de las semillas, mientras que los triacilgliceroles (TAG) representaron el 90 por ciento. La fracción cianolipídica estaba compuesta por el CL tipo III, el diester de 1-ciano-2-hidroximetilprop-3-en-1-ol. La investigación estructural de los componentes del aceite se logró mediante técnicas cromatografícas, (CCF, CC, GC-MS), y espectroscópicas (IR, RMN). El análisis por GC-MS mostró que los ácidos grasos tales como: ácidos cis-11-eicosenoico, cis-11-octadecanoico y eicosanoico fueron los únicos ácidos grasos esterificados ubicados en el extracto rico en CL tipo III. Siendo este el primer reporte de esta clase de productos naturales (CL) ubicados en las semilla de esta planta.


Assuntos
Ácidos Graxos/análise , Óleos , Sapindus/química , Sementes/química , Cromatografia Gasosa , Lipídeos/análise , Sementes , Análise Espectral , Sapindaceae/química
9.
Talanta ; 161: 71-79, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27769470

RESUMO

α-Bisabolol is a natural terpene produced by Eremanthus erythropappus and is widely used in cosmetics and pharmaceuticals due to its anti-inflammatory, antibacterial and antimycotic properties. Due to these applications, a control of composition and authenticity of commercial oils rich in this terpene is required, resulting in a demand for new methodologies for quality control. In this work a rapid and efficient method for quantification of α-bisabolol in the essential oil of E. erythropappus (candeia) using 1H NMR was developed, validated and compared to gas chromatography (GC) method. The quantification of α-bisabolol by 1H NMR was successfully achieved for most of the essential oil samples of E. erythropappus evaluated, except for those with a more complex composition. To circumvent this limitation a 2D NMR COSY contour map was used. This method proved to be a fast and efficient alternative, providing results with standard deviations SD<0.3%. All evaluated parameters (selectivity, linearity, accuracy/precision, repeatability, robustness and stability of analyte and internal standard in solution) gave satisfactory results. Using the 1H NMR signals at 5.36 and 5.13ppm, the limit of detection (LOD) and limit of quantification (LOQ) were 0.26 and 2.59mg, respectively. The results obtained by the 1H NMR method presented SD=0.59%, smaller than the value found for GC (SD=1.18%). Tukey tests have shown that the results obtained by 1H NMR and COSY methodology are similar to the obtained by the traditional GC-FID technique using external and internal standardization and normalization with 95% confidence.


Assuntos
Asteraceae , Óleos Voláteis/química , Sesquiterpenos/análise , Cromatografia Gasosa-Espectrometria de Massas , Limite de Detecção , Espectroscopia de Prótons por Ressonância Magnética
10.
Eur J Med Chem ; 124: 153-159, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27569196

RESUMO

Leishmaniasis is a neglected tropical disease (NTDs), endemic in 88 countries that affect more than 12 million people. Current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, the search for new effective and less toxic treatments is an urgent need. In this study, we report the synthesis of 3 new amide derivatives of hederagenin (22-24) with yields between 70% and 90%, along with 57 other derivatives of hederagenin (1-21, 25-60) carrying different groups at C-28 previously reported by our group, and the results of their in vitro ability to inhibit the growth of Leishmania infantum. Some derivatives (3, 4, 44, 49 and 52), showed activity at micromolar level and low toxicity against BGM and HepG2 cells. Moreover, the ability of hederagenin derivatives 3 (IC50 = 9.7 µM), 4 (12 µM), 44 (11 µM) and 49 (2 µM), to prevent proliferation of intracellular amastigote forms of L. infantum and their higher selectivity index and low toxicity compared to commercial positive drug control of choice (potassium antimonyl tartrate trihydrate) (IC50 = 80 µM, SI = 0.1), make these compounds promising candidates for the treatment of leishmaniasis.


Assuntos
Antiprotozoários/química , Antiprotozoários/farmacologia , Leishmania infantum/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Saponaria/química , Antiprotozoários/toxicidade , Células Hep G2 , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/parasitologia , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Ácido Oleanólico/toxicidade , Relação Estrutura-Atividade
11.
Chem Biodivers ; 13(8): 1008-17, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27389616

RESUMO

Although quinones present a large array of biological activities, a few studies on the herbicidal potential of 2,5-bis(alkyl/arylamino)-1,4-benzoquinones have been reported to date. In this work, starting from benzoquinone, 13 2,5-bis(alkyl/arylamino)-1,4-benzoquinones were prepared in 46 - 93% yield. The products were fully characterized by spectroscopic analyses and their phytotoxicity against Cucumis sativus and Sorghum bicolor seedlings was investigated. At 100 ppm, compounds caused 10 - 88% growth inhibition of the dicotyledonous species, whereas the monocotyledon was less affected. Most compounds exerted little inhibitory effect on a cyanobacterial model strain. However, at 100 µm, compounds 8 - 10 caused about 50% inhibition of algal growth, and compounds 1 and 2 reduced cell viability in the 1 - 10 µm range. The ability of benzoquinone derivatives to interfere with the light-driven ferricyanide reduction by isolated spinach chloroplasts was evaluated. Some substances showed a moderate effect as uncouplers, but no relationship was found between this property and their biological activity, indicating that the herbicidal effect is not associated with the inhibition of the photosynthetic electron transport chain. Phytotoxic compounds were not toxic to insects, strengthening the possibility that they may serve as lead for the development of eco-friendly herbicides.


Assuntos
Aminas/química , Benzoquinonas/farmacologia , Cucumis sativus/efeitos dos fármacos , Herbicidas/farmacologia , Sorghum/efeitos dos fármacos , Animais , Benzoquinonas/síntese química , Benzoquinonas/química , Cucumis sativus/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Herbicidas/síntese química , Herbicidas/química , Insetos/efeitos dos fármacos , Estrutura Molecular , Sorghum/crescimento & desenvolvimento
12.
J Biomed Mater Res A ; 104(12): 3015-3020, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27458927

RESUMO

Poly-ether-ether-ketone (PEEK) is currently introduced as an alternative material for orthopedic implants due to its biocompatibility and low elastic modulus compared to titanium. Also, a sulphonation treatment can functionalize PEEK to embed therapeutical substances. The objective of this work was to functionalize a PEEK film to incorporate novel lactam-based antibiofilms compounds. PEEK samples were functionalized by sulphuric acid treatment and then dissolved in dimethylsulfoxide, where lactams were added to be incorporated into the polymer. A dip-coating technique was used to synthesize a thin film on a glass-based substrate. The degree of sulfonation (DS) and the incorporation of lactams into sulphonated PEEK (sPEEK) were analyzed by Fourier transform infrared spectroscopy, nuclear magnetic resonance, thermogravimetric analysis (TGA), and scanning electron microscopy. A DS of 65% was obtained and TGA curves confirmed the presence of SO3 H and lactams in the sPEEK structure. The growth of Streptococcus mutans biofilm decreased on sPEEK surface containing lactams when compared to sPEEK free of lactams. That indicated the antibiofilm activity of those compounds was maintained after incorporation into sPEEK. Planktonic growth analysis showed no long distant effects of sPEEK containing lactams, indicating that no systemic effects should be expected upon clinical uses of medical devices produced with lactam-treated sPEEK. Results revealed that inclusion of lactams into sPEEK represents a good alternative for the production of biomaterials resistant to bacterial accumulation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3015-3020, 2016.


Assuntos
Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Cetonas/farmacologia , Lactamas/farmacologia , Polietilenoglicóis/farmacologia , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/química , Materiais Biocompatíveis/química , Humanos , Cetonas/química , Lactamas/química , Polietilenoglicóis/química , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/fisiologia , Propriedades de Superfície
13.
J Org Chem ; 81(15): 6883-6, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27347696

RESUMO

The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-ß-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal.


Assuntos
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/síntese química , Policetídeos/química , Aldeídos/química , Furanos/síntese química , Furanos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Quinolizinas/química , Estereoisomerismo , Compostos de Enxofre/química
14.
Org Biomol Chem ; 14(21): 4897-907, 2016 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-27163151

RESUMO

A stereoselective vinylogous aldol reaction of N-monosubstituted tetronamides with aldehydes is described. The procedure is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers (dr > 99 : 1) in high yields (70-90%). Experimental and computational studies suggest that the observed diastereoselectivity arises through anti-syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction.

15.
Eur J Med Chem ; 115: 257-67, 2016 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-27017553

RESUMO

A series of novel aryl-1H-1,2,3-triazol-4-yl methylester and amide derivatives of the natural product hederagenin was synthesized aiming to develop new antitumor agents, using Huisgen 1,3-dipolar cycloaddition reactions, with yields between 35% and 95%. The structures of all derivatives (2-31) were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic data. The cytotoxic activities of all compounds were screened against a panel of six human cancer cell lines using SRB assay. It was found that most of the compounds displayed higher levels of antitumor activities as compared to parent hederagenin. Compounds 4, 8 and 15 were the most potent against all human cancer cell lines. Furthermore, compound 11 was the most cytotoxic against cell HT29 showing EC50 = 1.6 µM and a selectivity index of 5.4.


Assuntos
Antineoplásicos/farmacologia , Ácido Oleanólico/análogos & derivados , Triazóis/química , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ácido Oleanólico/química
16.
Talanta ; 150: 97-103, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26838386

RESUMO

The authenticity and composition of commercial essential oils requires strict quality control. Due to the importance of α-pinene containing essential oils, a rapid and efficient method for quantification of this terpene in oils of eucalyptus, pink pepper and turpentine using (1)H NMR was developed and validated. All evaluated parameters (selectivity, linearity, accuracy/precision, repeatability, robustness, stability of analyte and internal standard in solutions) showed satisfactory results. The limit of detection (LOD) and limit of quantification (LOQ) were 0.1 and 2.5mg respectively. These values indicated that α-pinene was detected in 35 mg samples containing at least 0.3% of this compound. In addition, a minimum of 8% of α-pinene in the sample was required for quantification. Furthermore, the standard deviations found in the (1)H NMR methodology were less than 1% and were lower than those obtained by gas chromatographic analysis. Statistical tests have shown that the results obtained by (1)H NMR methodology are similar to those obtained by GC-FID technique using external and internal standardization and normalization within 95% confidence. R&R values lower than 10% have shown that all the methods are appropriate and the (1)H NMR method is suitable for quantification of α-pinene in samples of essential oils since this method possessed the smallest R&R (1.81) value.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Monoterpenos/análise , Óleos Voláteis/química , Cromatografia Gasosa-Espectrometria de Massas , Limite de Detecção , Modelos Lineares , Monoterpenos/química , Controle de Qualidade , Fatores de Tempo
17.
Eur J Med Chem ; 105: 57-62, 2015 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-26476750

RESUMO

In this study, a series of novel C-28 esters and amides derivatives of hederagenin (He) were designed and synthesized in attempt to develop potent antitumor agents. Their structures were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using a panel of six human cancer cell lines. Although most of the compounds displayed moderate to high levels of cytotoxic activity they were all more potent than the natural product He. The most active compounds had either an ethylpyrimidinyl (27) or an ethylpyrrolidinyl (28) substituent, with EC50 in the range of 1.1-6.5 µM for six human cancer cell lines. Notably, this corresponds to an approximately 30-fold times greater potency than He.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Ácido Oleanólico/análogos & derivados , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Relação Estrutura-Atividade
18.
Chem Biodivers ; 12(7): 987-1006, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26172321

RESUMO

Natural phytotoxins and their synthetic analogs are a potential source of new bioactive compounds for agriculture. Analogs of rubrolides, a class of γ-alkylidene-γ-lactones isolated from different ascidians, have been shown to interfere with the photosynthetic electron-transport chain, yet their activity needs to be improved. With this aim, ten 5-aryl-6-benzyl-4-bromopyridazin-3(2H)-ones were prepared in yields ranging from 44 to 88% by reaction of their correspondent γ-alkylidene-γ-lactones with NH2 NH2 . The structures of these rubrolide analogs were determined by (1) H- and (13) C-NMR, 2D-NMR (COSY and HETCOR), NOE difference, and MS techniques. These compounds were evaluated for their abilities of interfering with the light-driven reduction of ferricyanide by isolated spinach chloroplasts. Lactones with electron-withdrawing substituents in the para-position of the benzylidene ring were the most effective inhibitors. Characterization of the activity of 11b/11b' suggested a mechanism based on the interaction with the plastoquinone binding site of photosystem II. Addition of several compounds to the culture medium of a cyanobacterial model strain was found to inhibit algal growth. However, the relative effectiveness was not consistent with their activity in vitro, suggesting the occurrence of multiple targets and/or detoxyfication mechanisms. Indeed, the compounds showed differential effects on the heterotrophic growth of some crop species, Cucumis sativus and Sorghum bicolor. Pyridazin-3(2H)-ones 12e, 12i, and 12j, which have been found poorly active against the photosynthetic electron transport, were the most effective in inhibiting the growth of some weeds, Ipomoea grandifolia and Brachiaria decumbens, under greenhouse conditions.


Assuntos
Compostos Aza/farmacologia , Lactonas/farmacologia , Fotossíntese/efeitos dos fármacos , Compostos Aza/química , Brachiaria/efeitos dos fármacos , Brachiaria/crescimento & desenvolvimento , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Ipomoea/efeitos dos fármacos , Ipomoea/crescimento & desenvolvimento , Lactonas/química , Modelos Moleculares , Estrutura Molecular , Sorghum/efeitos dos fármacos , Sorghum/crescimento & desenvolvimento
19.
J Photochem Photobiol B ; 145: 11-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25748644

RESUMO

Natural products called rubrolides have been investigated as a model for the development of new herbicides that act on the photosynthesis apparatus. This study comprises a comprehensive analysis of the photosynthesis inhibitory ability of 27 new structurally diverse rubrolide analogues. In general, the results revealed that the compounds exhibited efficient inhibition of the photosynthetic process, but in some cases low water solubility may be a limiting factor. To elucidate their mode of action, the effects of the compounds on PSII and PSI, as well as their partial reaction on chloroplasts and the chlorophyll a fluorescence transients were measured. Our results showed that some of the most active rubrolide analogues act as a Hill reaction inhibitors at the QB level by interacting with the D1 protein at the reducing side of PSII. All of the active analogues follow Tice's rule of 5, which indicates that these compounds present physicochemical properties suitable for herbicides.


Assuntos
Furanos/química , Luz , Complexo de Proteína do Fotossistema I/antagonistas & inibidores , Complexo de Proteína do Fotossistema II/antagonistas & inibidores , Clorofila/química , Clorofila A , Cloroplastos/metabolismo , Transporte de Elétrons , Furanos/metabolismo , Furanos/toxicidade , Herbicidas/química , Herbicidas/metabolismo , Herbicidas/toxicidade , Fotossíntese/efeitos dos fármacos , Fotossíntese/efeitos da radiação , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Espectrometria de Fluorescência , Spinacia oleracea/metabolismo
20.
Pest Manag Sci ; 71(7): 1037-48, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25157959

RESUMO

BACKGROUND: Several 1,2,4,5-tetraoxanes were synthesised, and their herbicidal activity was tested against weeds and compared with the activity of commercial herbicides glyphosate and imazethapyr. RESULTS: The compounds were prepared by reacting carbonyl compounds with hydrogen peroxide under acid catalysis, affording 1,1-dihydroperoxides (36-91%) that were further converted into 1,2,4,5-tetraoxanes (10-52%) under similar reaction conditions. All products were evaluated against Sorghum bicolor and Cucumis sativus at 0.0125-1.0 mM, and several tetraoxanes caused >70% inhibition of the growth of roots and aerial parts. The most active products were evaluated against the weeds Sorghum arundinaceum, Euphorbia heterophylla, Brachiaria brizantha and Bidens pilosa. Some compounds were highly effective (>80% inhibition at 1.0 mM) against the weeds, showing activity comparable with that of glyphosate or imazethapyr. One of the tetraoxanes was selective, being inactive against dicotyledonous species while inhibiting the roots and aerial parts of monocotyledonous species by 92.9-97.5%, which is comparable with the effect of glyphosate. CONCLUSIONS: Tetraoxanes constitute a new class of effective herbicides with great potential for commercial development.


Assuntos
Herbicidas/síntese química , Plantas Daninhas/efeitos dos fármacos , Tetraoxanos/síntese química , Cucumis sativus/efeitos dos fármacos , Glicina/análogos & derivados , Glicina/farmacologia , Herbicidas/farmacologia , Ácidos Nicotínicos/farmacologia , Desenvolvimento Vegetal/efeitos dos fármacos , Sorghum/efeitos dos fármacos , Tetraoxanos/farmacologia
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