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This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor-acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.
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A method for the synthesis of 4-organoselanyl oxazinoindolone derivatives by the cascade cyclization of N-(alkoxycarbonyl)-2-alkynylindoles using iron(III) chloride and diorganyl diselenides as promoters was developed. This protocol was applied to a series of N-(alkoxycarbonyl)-2-alkynylindoles containing different substituents. The reaction conditions also tolerated a variety of diorganyl diselenides having both electron donating and electron withdrawing groups. However, the reaction did not work for diorganyl disulfides and ditellurides. The reaction mechanism seems to proceed via an ionic pathway and the cooperative action between iron(III) chloride and diorganyl diselenides is crucial for successful cyclization. We also found that using the same starting materials, by simply changing the electrophilic source to iodine, led to the formation of 4-iodo-oxazinoindolones. The high reactivity of Csp2 -Se and Csp2 -I bonds were tested under cross-coupling conditions leading to the preparation of a new class of functionalized indole derivatives. In addition, the absorption, emission and electrochemical properties of 4-organoselanyl oxazinoindolones showed an important relationship with the substituents of the aromatic rings. The advantages of the methodology include the use of electrophilic to promote the cyclization reaction and functionalization of the indole ring, and the electronic properties presented by the prepared compounds can be exploited as probes, analyte detectors and optical materials.
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Histoplasma capsulatum is a fungus that causes histoplasmosis. The increased evolution of microbial resistance and the adverse effects of current antifungals help new drugs to emerge. In this work, fifty-four nitrofurans and indoles were tested against the H. capsulatum EH-315 strain. Compounds with a minimum inhibitory concentration (MIC90) equal to or lower than 7.81 µg/mL were selected to evaluate their MIC90 on ATCC G217-B strain and their minimum fungicide concentration (MFC) on both strains. The quantification of membrane ergosterol, cell wall integrity, the production of reactive oxygen species, and the induction of death by necrosis-apoptosis was performed to investigate the mechanism of action of compounds 7, 11, and 32. These compounds could reduce the extracted sterol and induce necrotic cell death, similarly to itraconazole. Moreover, 7 and 11 damaged the cell wall, causing flaws in the contour (11), or changing the size and shape of the fungal cell wall (7). Furthermore, 7 and 32 induced reactive oxygen species (ROS) formation higher than 11 and control. Finally, the cytotoxicity was measured in two models of cell culture, i.e., monolayers (cells are flat) and a three-dimensional (3D) model, where they present a spheroidal conformation. Cytotoxicity assays in the 3D model showed a lower toxicity in the compounds than those performed on cell monolayers. Overall, these results suggest that derivatives of nitrofurans and indoles are promising compounds for the treatment of histoplasmosis.
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Cabernet Sauvignon grapes in Chile, mainly grown between the 30° S and 36° S, account for more than 30% of Chilean wine production, and yield wines with different characteristics which influence their quality. The aim of this study was to apply a liquid chromatography-mass spectrometry (LC-MS)-based metabolomic protocol to investigate the quality differentiation in a sample set of monovarietal wines from eight valleys covering 679 km of the north-south extension. All samples were produced using a standardized red winemaking process and classified according to a company categorization in two major groups: premium and standard, and each group in two subcategories. The results pointed out that N-containing metabolites (mainly small peptides) are promising biomarkers for quality differentiation. Moreover, the premium wines were characterized by higher amounts of anthocyanins and other glycosylated and acetylated flavonoids, as well as phenolic acids; standard quality wines, on the other hand, presented stilbenoids and sulfonated catabolites of tryptophan and flavanols.
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Tuberculosis has been described as a global health crisis since the 1990s, with an estimated 1.4 million deaths in the last year. Herein, a series of 20 1H-indoles were synthesized and evaluated as in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Furthermore, the top hit compounds were active against multidrug-resistant strains, without cross-resistance with first-line drugs. Exposing HepG2 and Vero cells to the molecules for 72 h showed that one of the evaluated structures was devoid of apparent toxicity. In addition, this 3-phenyl-1H-indole showed no genotoxicity signals. Finally, time-kill and pharmacodynamic model analyses demonstrated that this compound has bactericidal activity at concentrations close to the Minimum Inhibitory Concentration, coupled with a strong time-dependent behavior. To the best of our knowledge, this study describes the activity of 3-phenyl-1H-indole against Mtb for the first time.
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Antituberculosos/síntese química , Antituberculosos/farmacologia , Indóis/síntese química , Indóis/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Chlorocebus aethiops , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana/métodos , Relação Estrutura-Atividade , Células VeroRESUMO
To evaluate the natural occurrence of the plant growth-promoting bacterium Azospirillum brasilense and petunia plants, local strains were isolated and characterized by biochemical and molecular methods. Three strains were assessed in greenhouse conditions using Petunia × hybrida Ultra™. Treatments: Plants without bacterial inoculation or chemical fertilization; fertilized with NPK and KNO3 ; and independently inoculated with the strains 2A1, 2A2, and 2E1 by submerging their roots in a bacterial suspension (~106 CFU·ml-1 ). Root length, dry weight of roots and shoots, leaf area, leaf greenness, and nutrient content were evaluated. The number of days from transplanting to the opening of the first flower and the number of flowers per plant were also determined. As a result, five isolates were characterized as A. brasilense, showing the capacity to produce indoles and siderophores, to solubilize phosphate, nitrogenase activity, and nifH-PCR amplification. In general, all the parameters of the plant assay were improved in plants inoculated with A. brasilense, with variations among the strains, as well as the onset of flowering and the number of flowers per plant, compared with uninoculated or fertilized plants. This is the first report on the natural occurrence of A. brasilense in petunia with the capacity to improve plant growth and flowering.
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Azospirillum brasilense/fisiologia , Magnoliopsida/microbiologia , Petunia/crescimento & desenvolvimento , Petunia/microbiologia , Desenvolvimento Vegetal , Azospirillum brasilense/genética , Biomassa , Folhas de Planta/microbiologia , Raízes de Plantas/microbiologiaRESUMO
Acute promyelocytic leukemia (APL) is associated with PML-RARα oncogene, which is treated using all-trans retinoic acid (ATRA)-based chemotherapy. However, chemoresistance is observed in 20-30% of treated patients and represents a clinical challenge, raising the importance of the development of new therapeutic options. In the present study, the effects of three synthetic cyclopenta[b]indoles on the leukemia phenotype were investigated using NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Among the tested synthetic cyclopenta[b]indoles, compound 2, which contains a heterocyclic nucleus, was the most active, presenting time-dependent cytotoxic activity in the µM range in APL cells, without cytotoxicity for normal leukocytes, and was selected for further characterization. Compound 2 significantly decreased clonogenicity, increased apoptosis, and caused cell cycle arrest at S and G2/M phases in a drug concentration-dependent manner. Morphological analyses indicated aberrant mitosis and diffuse tubulin staining upon compound 2 exposure, which corroborates cell cycle findings. In the molecular scenario, compound 2 reduced STMN1 expression and activity, and induced PARP1 cleavage and H2AX and CHK2 phosphorylation, and modulated CDKN1A, PMAIP1, GADD45A, and XRCC3 expressions, indicating reduction of cell proliferation, apoptosis, and DNA damage. Moreover, in the in vivo tubulin polymerization assay, NB4 and NB4-R2 cells showed a reduction in the levels of polymerized tubulin upon compound 2 exposure, which indicates tubulin as a target of the drug. Molecular docking supports this hypothesis. Taken together, these data indicated that compound 2 exhibits antileukemic effects through disrupting the microtubule dynamics, identifying a possible novel potential antineoplastic agent for the treatment of ATRA-resistant APL.
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Antineoplásicos/farmacologia , Ciclopentanos/química , Indóis/farmacologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Microtúbulos/metabolismo , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Indóis/química , Microtúbulos/efeitos dos fármacos , Mitose/efeitos dos fármacos , Modelos Moleculares , Estatmina/biossíntese , Ensaio Tumoral de Célula-TroncoRESUMO
Objective: the development of new drugs against Methicillin-resistant Staphylococcus aureus is a priority to the World Health Organization. So, the objective of this study was to evaluate the antibacterial activity and toxicity of 5-bromo-3-((4-methoxyphenyl) sulfenyl)-1H-indole (3b) against MRSA. Methods: minimum inhibitory concentration (MIC) of 3b was determined against S. aureus ATCC 29213 and 43 clinical isolates. The time-kill assay was performed for 9 isolates. Analysis of variance followed by the post hoc Bonferroni test was used for the statistical tests. Results and conclusions: the MIC50 and MIC90 of 3b were 4 µg.mL-1 and 16 µg.mL-1 respectively. In time-kill assay, the 3b showed bactericidal activity to all evaluated isolates at concentrations of 1xMIC and 2xMIC and the re-growth effect was not observed. About the toxicity tests, 3b has not presented cytotoxicity, mutagenicity, or allergenicity. 3b had particularly good activity against MRSA demonstrating high potential for the development of new antimicrobials products.
Objetivo: o desenvolvimento de novos antimicrobianos contra Staphylococcus aureus resistentes à meticilina (MRSA) é uma prioridade para a Organização Mundial da Saúde. Então, o objetivo desse estudo foi avaliar a atividade antibacteriana e a toxicidade do 5-bromo-3-((4-metoxifenil) sulfenil)-1H-indol (3b) contra MRSA. Métodos: a concentração inibitória minima de 3b foi determinada contra S. aureus ATCC 29213 e 43 isolados clínicos. O ensaio de curva de morte foi realizado para nove isolados. Análise de variância seguida pelo teste post hoc Bonferroni foi usada para testes estatísticos. Resultados e conclusões: a MIC50 e MIC90 do 3b foi 4 µg.mL-1 e 16 µg.mL-1, respectivamente. No ensaio de curva de morte, o 3b demonstrou atividade bactericida contra todos os isolados avaliados na concentração de 1xMIC e 2xMIC e o recrescimento não foi observado. Em relação aos testes de toxicidade, 3b não apresentou citotoxicidade, mutagenicidade ou alergenicidade. 3b apresentou atividade particularmente interessante contra MRSA, demonstrando alto potencial para o desenvolvimento de novos produtos antimicrobianos.
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Staphylococcus aureus , Staphylococcus aureus Resistente à Meticilina , Resistência a Meticilina , Anti-Infecciosos , AntibacterianosRESUMO
Despite the success achieved in the treatment of acute lymphoblastic leukemia (ALL), the search for new drugs featuring selectivity against leukemia cells and effectiveness to prevent relapsed ALL is still highly desirable. Here, we described the synthesis of several novel 3-substituted and 3,6-disubstituted-2-carboalkoxy indoles followed by the elucidation of their mechanism of action and in vivo anti-leukemia efficacy. The synthesis of 3-substituted-2-carboalkoxy indoles relied on two Heck arylations of methyl acrylate and methyl cinnamates respectively, to generate ß,ß-disubstituted acrylates followed by an efficient Cadogan-Sundberg reaction of these latter intermediates. The method developed led to the synthesis of twenty-one novel functionalized indoles. Of these, indole 20 showed selective cytotoxicity against leukemia cells at the nanomolar scale, and, therefore, it was selected for the investigation of its mechanism of action. Indole 20 was found to target tubulin leading to G2/M cell cycle arrest, DNA damage and apoptosis. Indole 20 decreased ß-tubulin protein in leukemia cells in a time-dependent manner and induced depolymerization of the microtubule network in Hela cells, thus fully characterizing its microtubule destabilizer activity. The connectivity map analysis of HL60 promyelocytic leukemia cells treated with indole 20 revealed a transcriptional profile similar to that of cells treated with prostaglandins, apparently due to the induction of cellular differentiation as addressed by the expression of CD11 and CD14 markers. Finally, indole 20 given intraperitoneally, at 10â¯mg/kg, 5x/week significantly prolonged the overall survival of NOD/SCID mice transplanted with RS4; 11â¯B-ALL cells.
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Antineoplásicos/química , Antineoplásicos/uso terapêutico , Indóis/química , Indóis/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Cinamatos/síntese química , Cinamatos/química , Cinamatos/uso terapêutico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células HL-60 , Células HeLa , Humanos , Indóis/síntese química , Camundongos Endogâmicos NOD , Camundongos SCIDRESUMO
In this work, a series of 2-chalcogenylindoles was synthesized by an efficient methodology, starting from chalcogenoalkynes, including a previously unreported tellurium indole derivative. For the first time, these 2-substituted chalcogenylindoles were obtained in the absence of metal catalyst or base, under thermal conditions only. In addition, the results described herein represent a methodology with inverse regioselectivity for the chalcogen functionalization of indoles.
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The objective of this work was to obtain and evaluate anti-inflammatory in vitro, in vivo and in silico potential of novel indole-N-acylhydrazone derivatives. In total, 10 new compounds (3a-j) were synthesized in satisfactory yields, through a condensation reaction in a single synthesis step. In the lymphoproliferation assay, using mice splenocytes, 3a and 3b showed inhibition of lymphocyte proliferation of 62.7% (±3.5) and 50.7% (±2), respectively, while dexamethasone presented an inhibition of 74.6% (±2.4). Moreover, compound 3b induced higher Th2 cytokines production in mice splenocytes cultures. The results for COX inhibition assays showed that compound 3b is a selective COX-2 inhibitor, but with less potency when compared to celecoxib, and compound 3a not presented selectivity towards COX-2. The molecular docking results suggest compounds 3a and 3b interact with the active site of COX-2 in similar conformations, but not with the active site of COX-1, and this may be the main reason to the COX-2 selectivity of compound 3b. In vivo carrageenan-induced paw edema assays were adopted for the confirmation of the anti-inflammatory activity. Compound 3b showed better results in suppressing edema at all tested concentrations and was able to induce an edema inhibition of 100% after 5â¯h of carrageenan injection at the 30â¯mgâ¯kg-1 dosage, corroborating with the COX inhibition and lymphoproliferation results. I addition to our experimental results, in silico analysis suggest that compounds 3a and 3b present a well-balanced profile between pharmacodynamics and pharmacokinetics. Thus, our preliminary results revealed the potentiality of a new COX-2 selective derivative in the modulation of the inflammatory process.
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Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Hidrazonas/química , Hidrazonas/farmacologia , Acilação , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Carragenina , Linhagem Celular , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/enzimologia , Feminino , Humanos , Hidrazonas/síntese química , Hidrazonas/uso terapêutico , Indóis/síntese química , Indóis/química , Indóis/farmacologia , Indóis/uso terapêutico , Camundongos Endogâmicos BALB C , Simulação de Acoplamento MolecularRESUMO
ABSTRACT The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.
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Animais , Masculino , Feminino , Ratos , Triptaminas/farmacologia , Salicilatos/farmacologia , Edema/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Peptídeos/efeitos dos fármacos , Fatores de Tempo , Carragenina , Triptaminas/toxicidade , Salicilatos/toxicidade , Ratos Wistar , Mediadores da Inflamação , Modelos Animais de Doenças , Edema/induzido quimicamente , Membro Posterior , Anti-Inflamatórios/toxicidadeRESUMO
Resumen El uso de Rizobacterias promotoras de crecimiento vegetal (PGPR, por sus siglas en ingles) constituye una alternativa al uso de fertilizantes químicos favoreciendo el rendimiento de los cultivos. La presente investigación tuvo como objetivo la búsqueda, selección y caracterización de PGPB de los géneros Azotobacter, Azospirillum y Pseudomonas nativas de la rizósfera de cultivos de Ipomoea batatas de zonas productoras representativas del Caribe Colombiano. Los aislados seleccionados se caracterizaron molecularmente y realizaron pruebas de solubilización de fósforo, producción de índoles y reducción de acetileno. Las cepas fueron probadas a nivel de invernadero en plántulas de Ipomoea batatas producidas in vitro en las que se evaluó la altura, longitud radicular, masa seca de la parte aérea y radicular. Asociada a la rizósfera de Ipomoea batatas se obtuvieron cepas de Azotobacter vinelandii, Azotobacter chroococcum, Azospirillum lipoferum, Azospirillum brasilense y Pseudomonas denitrificans, las cepas fueron capaces de solubilizar fósforo, producir índoles y reducir acetileno. Se obtuvo incrementos en parámetros de crecimiento como longitud radicular, altura, peso seco aéreo y radicular en plántulas de Ipomoea batatas en invernadero con la inoculación de las bacterias seleccionadas frente a plántulas sin inocular. Los resultados catalogan a los aislados obtenidos como posibles microorganismos con potencial como biofertilizantes en batata.
Abstract The use of plant growth promoting Rhizobacteria (PGPR) is an alternative to replace chemical fertilizers for the cultivation of agricultural crops. The aim of this research was to search, selection and characterization of PGPR from the genus Azotobacter, Azospirillum and Pseudomonas natives from sweet potato (Ipomoea batatas) plants and rhizosphere of representative production regions of the Colombian Caribbean. Selected isolates were identified by molecular methods and they were screenedin vitrofor activities related to plant growth such as phosphate solubilization, indole production and acetylene reduction. The strains were tested in the greenhouse on plants of Ipomoea batatas produced in vitro. The height, root length, dry mass of the shot and root were evaluated. Associated with sweet potato crop us finded strains identificated as Azotobacter vinelandii, Azotobacter chroococcum, Azospirillum lipoferum, Azospirillum brasilense and Pseudomonas denitrificans. The strains were able to solubilize phosphate, synthesize indole-3-acetic acid (IAA) and reduce acetylene. The inoculation of bacteria selected increased growth parameters such as root length, height, dry weight root and shoot in plants of sweet potato in greenhouse. Those results catalog to the isolated obtained as possible microorganisms with potential as biofertilizers in sweet potato.
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ABSTRACT The capacity to solubilize phosphate and to produce indole compounds Indole Acetic Acid type, was evaluated in 15 strains isolated from castor bean lignocellulosic residues (Ricinus communis). To determine the solubilizing activity of phosphates a qualitative test by using Pikovskaya culture medium was employed and for the evaluation of the production of indole compounds (IAA) a Salkowsky colorimetric analysis technique was applied. Among the microorganisms tested, the Bacillus pumilus GIBI 206 demonstrated capacity to solubilize phosphates and Bacillus subtilis GIBI 200 showed of capacity to solubilize phosphates and to produce Indoleacetic Acid (IAA). To determine the effect of the Bacillus subtilis strain on germination and growth promotion, tomato seeds (Solanum lycopersicum 'Santa Clara') were inoculated; the inoculation of the seeds along with the microorganism revealed statistically significant differences, during the germination stage compared to the control treatment. Nevertheless, it revealed a positive influence on the development of tomato plants, originating a significant increase on the mass and length of its stem and root. The results of this research offer the possibility of using the Bacillus subtilis as a growth promoter in tomato seedlings and in the formulation of bio-products.
RESUMEN La capacidad para solubilizar fosfatos y producir compuestos indólicos del tipo Ácido Indol Acético, se evaluó en 15 cepas aisladas de residuos lignocelulósicos de higuerilla (Ricinus communis). Para determinar la actividad solubilizadora de fosfatos se realizó una prueba cualitativa utilizando medio de cultivo Pikovskaya y para evaluar la producción de compuestos indólicos (AIA) se empleó la técnica colorimétrica de Salkowsky. Entre los microorganismos evaluados, Bacillus pumilus GIBI 206 mostró tener la capacidad para solubilizar fosfatos y Bacillus subtilis GIBI 200 evidenció capacidad para solubilizar fosfatos y producir Ácido Indolacético (AIA). Para determinar el efecto de la cepa Bacillus subtilis sobre la germinación y promoción de crecimiento, se inoculó en semillas de tomate (Solanum lycopersicum cultivar Santa Clara); la inoculación de las semillas con el microorganismo no mostró diferencias estadísticamente significativas en el tiempo de germinación en comparación con el tratamiento control, sin embargo mostró influir positivamente en el desarrollo de las plantas de tomate generando un aumento significativo sobre la masa y longitud del tallo y de la raíz. Los resultados de esta investigación ofrecen la posibilidad de utilizar a Bacillus subtilis como promotora de crecimiento en plántulas de tomate y en la formulación de bioinsumos.
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A novel series of twenty 3-thiocyanato-1H-indoles, carrying diversification at positions N-1, C-2 and C-5 of the heterocyclic core, were synthesized; their antiproliferative activity against four human cancer cell lines (HL60, HEP-2, NCI-H292 and MCF-7) was evaluated, employing doxorubicin as positive control. Indole, N-methylindole and 2-(4-chlorophenyl)-N-methylindole demonstrated to be essentially inactive, whereas several of their congener 3-thiocyanato-1H-indoles displayed good to excellent levels of potency (IC50 ≤ 6 µM), while being non-hemolytic. N-Phenyl-3-thiocyanato-1H-indole and 1-methyl-2-(4-chlorophenyl)-3-thiocyanato-1H-indole showed good to high potency against all the cell lines. On the other side, the N-(4-chlorophenyl)-, 2-(4-chlorophenyl)- and 2-phenyl- 3-thiocyanato-1H-indole derivatives were slightly less active against the test cell lines. Overall, these results suggest that the indole-3-thiocyanate motif can be suitably decorated to afford highly cytotoxic compounds and that the substituted indole can be employed as a useful scaffold toward more potent compounds.
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Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Indóis/síntese química , Indóis/farmacologia , Antineoplásicos/química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Ensaios de Seleção de Medicamentos Antitumorais , Hemólise/efeitos dos fármacos , Humanos , Indóis/química , Indóis/toxicidadeRESUMO
En las últimas décadas, la agricultura colombiana se ha visto afectada por la reducción de la productividad en las zonas hortícolas, el incremento de los costos de producción y la dependencia del uso de productos químicos, produciendo un daño irreversible al medio ambiente y la calidad de vida de productores y consumidores. El objetivo de investigación fue evaluar el efecto de rizobacterias promotoras del crecimiento vegetal del género Pseudomonas sp. sobre Lactuca sativa cultivar White Boston como solubilizadoras de roca fosfórica. El estudio se realizó en el Centro de Investigación Tibaitatá (Corpoica) ubicado en Mosquera (Cundinamarca-Colombia). Los resultados demostraron que las cepas tienen la capacidad intrínseca para solubilizar fuentes de fósforo de baja solubilidad como la roca fosfórica. La aplicación de inoculantes con base en las cepas: Pseudomonas fluorescens FR1, Pseudomonas sp., UVLO27 y Pseudomonas sp. LEAV18 arrojaron los mejores resultados. Las cepas Pseudomonas sp. FR2, UVLO27 y K35, tienen la capacidad de producir índoles y sideróforos. El experimento en invernadero evidenció que las cepas Pseudomonas fluorescens FR1, Pseudomonas sp. FR2 y UVLO27 incrementaron de manera significativa (P<0.05) la biomasa y el desarrollo de las plantas. El uso de rocas fosfóricas representa una alternativa económica y ecológica viable, en sistemas de agricultura sostenible.
In the last decades, Colombian agriculture has been affected by the reduction in productivity in horticultural areas, increase in production costs and the dependence of chemical products usage, causing and irreversible damage to environment and producers and consumers life quality. The aim of this research was to evaluate the effect of plant growth promoting rhizobacteria of the genus Pseudomonas sp. under Lactuca sativa cultivar White Boston as phosphate rock solubilizing bacteria. The study took place in the Research Centre Tibaitatá-Corpoica, located in Mosquera (Cundinamarca-Colombia). Results demonstrated that the strains have an intrinsic capacity to solubilize low solubility phosphorus sources as phosphate rock. Inoculants application based on: Pseudomonas fluorescensFR1, Pseudomonas sp., UVLO27 and Pseudomonas sp. LEAV18 strains displayed the best results. The strains Pseudomonas sp. FR2, UVLO27 and K35, are capable of producing indoles and siderophores. The green house experiment showd that strain Pseudomonas fluorescens FR1, Pseudomonas sp. FR2 of phosphate rocks represents a viable economic and ecological alternative in sustainable agriculture systems.
RESUMO
La sarna polvosa de la papa es causada por el patógeno Spongospora subterranea, que disminuye la calidad y producción de tubérculos y facilita la entrada de otros patógenos. Esta enfermedad afecta las principales zonas productoras del mundo, debido a la falta de tratamientos efectivos contra el patógeno y al comercio de tubérculos-semilla infectados. Algunas investigaciones indican que los agentes biocontroladores podrían contribuir a reducir la actividad de S. subterranea a través de efectos sobre la viabilidad de sus quistosoros o mediante efectos estimulantes del crecimiento de la planta. En este estudio se emplearon bacterias aisladas del interior de raíz, rizósfera y superficie de tubérculos de un cultivo de papa ( Solanum tuberosum variedad Diacol Capiro) y seleccionadas por su capacidad para producir indoles totales y quitinasas. En estudios paralelos se determinó su capacidad para promover la velocidad de germinación en brotes de tubérculos o para controlar S. subterranea en raíces y promover el crecimiento vegetal de plántulas en invernadero. La mayoria de los aislamientos evaluados incrementraron la longitud de brotes de tubérculos en el laboratorio. En el invernadero, en suelo no estéril y en presencia del patógeno, se encontró que 2 de los 10 aislamientos seleccionados por su capacidad para producir indoles totales y quitinasas, presentaron promoción de crecimiento vegetal y posible biocontrol del patógeno. Estos resultados sugieren un gran potencial para la selección de microorganismos biocontroladores y desarrollo de bioproductos a partir de recursos microbiológicos locales.
The powdery scab of potato is caused by the pathogen Spongospora subterranea which reduces the quality and yield of tubers and facilitates the establishment of other pathogens. This disease affects main potato production zones in the world, because there is not a completely effective and available control method against the disease, and due to the trading of infested seed tubers. Some research suggests that biological control agents could reduce the activity of S. subterranea through effects on the viability of their cystosoris or zoospores or by stimulating plant growth. In this research, bacteria previously isolated, from inside the roots, the rhizosphere and tuber peel of potato plants (Solanum tuberosum var. Diacol Capiro), were used, and then selected according to their capacity for producing total indoles and chitinases. Here was tested in parallel studies the capacity of nine bacterial isolates differing in total indole and chitinase production, for its capacity at increasing tuber sprout length and in promoting plant growth and biocontrol of S. subterranea . Inoculated in excised minitubers in laboratory most indole producing isolates tested resulted in increased tuber sprout length. In the greenhouse assay, in non-sterile soil and under a high pathogen pressure, two of the ten isolates selected because for their ability to produce total indoles and chitinases, showed plant growth promotion and possible biocontrol of the pathogen. These results suggest a great potential for the selection of biocontrol microorganisms and the development of new bioproducts from local microbial resources.
Assuntos
Crescimento , Reguladores de Crescimento de Plantas , Conservantes de Alimentos , Grupos ControleRESUMO
Como parte de las estrategias de una agricultura sostenible, se hace necesario disminuir el uso de fertilizantes nitrogenados de síntesis, mediante la utilización de los biofertilizantes. En particular, los géneros Azotobacter y Azospirillum son utilizados como agentes promotores de crecimiento vegetal debido a su capacidad para fijar nitrógeno atmosférico y producir hormonas de tipo indólico. Por tal razón, en este estudio se aislaron bacterias diazotróficas de los géneros Azotobacter y Azospirillum a partir de la rizósfera de cultivos de algodón en el Espinal (Tolima). Las poblaciones microbianas se caracterizaron fenópicamente en los medios de cultivo semiespecificos: Ashby y LG (Azotobacter sp.) y NFb, LGI y Batata (Azospirillum sp.). La promoción de crecimiento vegetal se determinó mediante la actividad de la enzima nitrogenasa por medio de la técnica de reducción de acetileno y producción de Ãndoles por el método colorimérico de Salkowsky. Se obtuvieron 9 aislamientos tentativos de Azotobacter sp. y 4 de Azospirillum sp. Se presentaron diferencias significativas en la prueba de reducción de acetileno con las cepas presuntivas de Azotobacter sp.: NAT 9 (206.43 nmol C2H2 mL-1.h-1), NAT 4, (292.77 nmol C2H2 mL-1.h-1), y NAT 6 (460.60 nmol C2H2 mL-1.h-1) y en la producción de índoles de las cepas NAT 19 (19.87 íµg.mL-1) y NAT 13 (20.08 íµg.mL-1). Por su eficiencia In vitro en la promoción de crecimiento vegetal se seleccionaron las cepas NAT9, NAT4, NAT6, NAT19 y NAT13 para ser evaluadas como principio activo en futuros inoculantes para el algodón en esta zona del departamento del Tolima.
As part of strategies for sustainable agriculture, it is necessary to reduce the use of synthetic nitrogen fertilisers through the use of biofertilisers. In particular, the genera Azotobacter and Azospirillum are used as plant growth promoters because of their ability to fix atmospheric nitrogen and indolic type hormones. For this reason, in this study were isolated diazotrophic bacteria of the genera Azotobacter and Azospirillum from the rhizosphere of cotton crops in Espinal (Tolima). The microbial populations were characterized phenotypically in specific semi culture media: Ashby and LG (Azotobacter sp.) and NFb, LGI and Batata (Azospirillum sp.). The promotion of plant growth was determined by the enzyme nitrogenase activity through acetylene reduction technique and production of indoles by the salkowsky colorimetric method. 9 isolates were obtained tentative Azotobacter sp. and 4 of Azospirillum sp. Significant differences in acetylene reduction test with presumptive strains of Azotobacter sp.: NAT 9 (206.43 nmol C2H2 mL-1.h-1), NAT, 4, (292.77 nmol C2H2 mL-1.h-1), and NAT 6 (460.60 nmol C2H2 mL-1.h-1) and indole production strains NAT 19 (19.87 µg.mL-1) and NAT 13 (20.08 µg.mL-1). In vitro efficiency in promoting plant growth were selected strains NAT9, NAT4, NAT6, NAT19 and NAT13 to be evaluated as active in future inoculants on cotton in this part of the department of Tolima.