Efecto antiparasitario de los extractos etanólico y etéreo de Ficus obtusifolia kunth (MORACEAE), frente a parásitos de clase nemátodos (Toxocara cati y Toxocara canis)

El conocimiento de la medicina natural constituye una valiosa fuente de información y orientación para realizar tamizajes fitoquímicos y farmacológicos. Este conocimiento ha generado en los últimos años, un auge en el estudio fitoquímico. Por ende, en nuestro país, se ha intensificado la práctica de la disciplina fitoquímica, lo cual constituye también una forma de recuperar nuestro acervo cultural en peligro, causado por la deforestación, migración del campo a la ciudad y otros factores.1. INTRODUCCIÓN 8 2. PLANTEAMIENTO DEL PROBLEMA 10 3. JUSTIFICACIÓN 11 4. OBJETIVOS 13 4.1 Objetivo General 13 4.2 Objetivos Específicos 13 5. MARCO TEORICO 14 5.1 Parásitos 14 5.2 Bacterias 15 5.3 Aspectos Generales de la Familia Moraceae: 19 6. ANTECEDENTES 23 6.1. Investigaciones realizadas a la Especie Ficus obtusifolia kunth 23 6.2 FICUS (HIGUERÓN): 23 6.3 Metabolitos secundarios. 24 6.4 Actividad Biológica DL50 50 7. METODOLOGÍA 52 7.1 Recolección y secado del material vegetal 53 7.2Análisis Fitoquímico preliminar 54 7.3 Recolección y obtención de los huevos de Parásito 55 7.4 Análisis actividad bactericida 60 7.5 Análisis estadístico 66 8. Resultados y analisis de los resultados 68 8.1 Análisis fitoquímico en hojas de los extractos etanólico y etéreo crudo sin clorofila 68 8.2 Análisis fitoquímico en hojas y fruto de los extractos etéreo crudo 70 8.3 Resultados de esteroles en el extracto etéreo para hojas y fruto en cromatografía de capa delgada 72 8.4 Resultados de Actividad bactericida de los extractos etanólicos de hojas y fruto en una concentración de 50.000 ppm y comparación con Muller Hilton73 8.5 Resultados de Actividad bactericida de los extractos etéreos de hojas y fruto en una concentración de 50.000 ppm y comparación con Muller Hilton 74 8.7 Resultados de la actividad antihelmíntica en Parásitos adultos Toxocara Canis de los extractos etanólicos y etéreos de hojas y fruto. 76 8.8 Resultados del análisis estadístico factorial en huevos de Parásitos Toxocara canis y Toxocara catis en los extractos etanólico y etéreo de hojas y fruto. 78 8.9 Resultados de la actividad biológica de DL50 85 9. CONCLUSIONES 92PregradoQuímic

Estudio químico y biológico de especies del género Azorella

143 p.El presente estudio tuvo por finalidad aislar e identificar los metabolitos mayoritarios a partir de algunas plantas del género Azorella, (A.spinosa, A. madreporica) cuyas especies forman parte de la familia Apiaceae, además de obtener derivados semisintéticos en la medida que fue posible y probar la actividad biológica de estos compuestos. Investigaciones realizadas en otros géneros de Azorella han permitido la identificación de varios compuestos diterpenicos del tipo azorellano y mulinano, algunos de estos diterpenos han sido responsables de distintas actividades biológicas, tales como antibacteriana, antiinflamatoria, inhibición de la acetilcolinesterasa, entre otras. El estudio químico de las partes aéreas de la especie A. spinosa permitió aislar diterpenos, un triterpeno, cumarina e isoflavonas. A partir del extracto etéreo fueron aislados cuatro diterpenos dos de ellos reportados previamente en literatura, en otras especies 13α-hidroxiazorellano, ácido mulinólico y dos compuestos nuevos 2-acetoxi-13-hidroxi-mulin-11-eno, 2-acetoxi-mulin-11,13-dieno, a partir de 2-acetoxi-13-hidroxi-mulin-11-eno se obtuvo el compuesto hidrolizado 2,13-dihidroxi-mulin-11-eno. Por otra parte del extracto metanólico se aisló un triterpeno, que resulto ser la lactona del ácido ursólico siendo este compuesto nuevo en esta especie pero ya reportado en otras plantas, de este mismo extracto se aisló quercetina y 7-hidroxicumarina.A partir del estudio químico de la A. madreporica fueron aisladas tres isoflavonas las cuales corresponden a alpinumisoflavona, licoisoflavona A y angustona C, compuestos reportados por primera vez en esta especie. A partir de la alpinumisoflavona se obtuvo el derivado diacetilado 4´,4´´-diacetoxi-alpinumisoflavona y de la acetilación de licoisoflavona se obtuvo el derivado monoacetilado 7-acetoxi-licoisoflavona A. Todos los compuestos aislados que resultaron ser nuevos o informados por primera vez en estas especies, como también los derivados semisintéticos preparados, fueron evaluados mediante el ensayo de microdilución en microplacas como agentes antibacterianos frente a Escherichia coli, Acinetobacter baumanni, Pseudomonas aeuroginosa y Staphilococcus aureus. Solo las isoflavonas alpinumisoflavona y licoisoflavona A fueron activas y selectivos sobre E. coli. Los diterpenos 2-acetoxi-13-hidroxi-mulin-11-eno, 2-acetoxi-mulin-11,13-dieno y el derivado 2,13-dihidroxi-mulin-11-eno, fueron evaluados en el ensayo de inhibición de la enzima acetilcolinesterasa (AChE) y la butirilcolinesterasa (BuChE) y sobre la actividad antioxidante empleando el ensayo DPPH. Por otro lado, el extracto metanólico de A. spinosa recolectada en la zona de Constitución (Región del Maule) y tres extractos metanólicos de A. monantha recolectadas en tres localidades distintas Paso Vergara y Enladrillado (Región del Maule), y Torres del Paine (Región de Magallanes) se evaluaron sobre todas las actividades biológicas anteriormente descritas, incluyendo la actividad antiplaquetaria, siendo los extractos de A. spinosa y A. monantha (Paso Vergara) las que mostraron mejores resultados./ABSTRACT: The aim of this study was to isolate and to identify the main metabolites from some plants of the Azorella (A.spinosa, A. madreporica) genre whose species are part of the Apiaceae family. Also, this study helped to obtain semisynthetic derivatives as possible as far and to test the biological activity of these compounds. Research in other Azorella genres have allowed the identification of several diterpene compounds of the mulinane and azorellane type. Some of these diterpenes have been responsible of the various biological activities such as antibacterial, anti-inflammatory, inhibition of acetylcholinesterase, and others. The chemical study of the aerial parts of the species A. spinosa allowed to isolate diterpenes, triterpenes, isoflavones and coumarin. From the ethereal extract, four diterpenes were isolated, two of them were previously reported in literature, in other species like the 13α-hydroxyazorellane and mulinolic acid, and the other two new compounds, 2-acetoxy-13-hydroxy- mulin-11-en, 2-acetoxy-mulin 11,13-diene, starting from the 2-acetoxy-13-hydroxy- mulin-11-en compound was obtained the 2,13-dihydroxy-mulin-11-en. By the other side, a triterpene was isolated from the methanol extract, which has proved to be the lactone of the ursolic acid being this a new compound in this specie but already reported in other plants. From the same extract was isolated quercetin and 7-hydroxycoumarin. From the chemical study of the A. madreprica, three isoflavones were isolated which correspond to alpinumisoflavone, angustone C and licoisoflavone A, compounds reported by the first time in this species. Starting from the alpinumisoflavone, the diacetyl derivative was obtained 4',4''-diacetoxy-alpinumisoflavoe and from the licoisoflavone acetylation, 7-acetoxy-licoisoflavone A monoacetylated derivative was obtained. All these compounds were elucidated using conventional spectroscopic techniques and by mean of the comparison with literature data. All those isolated compounds were found to be new or reported by first time in these species. Also, semisynthetic derivatives were evaluated by the microdilution in assay microplates as antibacterial against Escherichia coli, Acinetobacter baumanni, Pseudomonas aeruginosa and Staphylococcus aureus. Only the alpinumisoflavone and licoisoflavone A isoflavones were active and selective over the E. coli. The diterpenes 2-acetoxy-13-hydroxy-mulin-11-en, 2-acetoxy-mulin-11,13-diene and 2,13-dihydroxy mulin-11-en derivative were evaluated in the inhibition assay of the acetylcholinesterase (AChE) enzyme and the butyrylcholinesterase (BuChE). Also, the antioxidant activity were evaluated using the DPPH assay.By the other hand, the methanolic extract of A. spinosa collected from Constitución zone (Region of Maule) and the three methanol extracts of A. monantha collected from three different locations like Paso Vergara and Enladrillado (Region of Maule), and Torres del Paine (Region of Magallanes) were evaluated on over all the biological activities described above, including antiplatelet activity, being the extracts of A. spinosa and A. monantha (Paso Vergara) that showed the best result

Clinical and Epidemiological Characteristics of Streptococcus suis Infections in Catalonia, Spain

Introduction: Streptococcus suis (S. suis) is a human zoonotic pathogen of occupational origin, with infection acquired through contact with live pigs or pig meat. Pig farming is one of Catalonia's biggest industries and as a result this region of Spain has one of the highest density pig populations per km2. The aim of our study was to describe the infections caused by S. suis occurring in that area over a 9-year period. Materials and Methods: A retrospective, multi-center study was carried out by searching records from 15 hospitals in Catalonia for the period between 2010 and 2019. Results: Over the study period altogether nine cases of S. suis infection were identified in five hospitals, with five of these cases occurring in the 2018-2019 period. The mean age of patients was 48 ± 8.9 years and all of them were males. Five patients (55.6%) worked in pig farms. The most frequent manifestation of infection was meningitis (5 cases; 55.6%) followed by septic arthritis (3 cases; 33.3%). None of the patients died at 30 days; nonetheless, 4 developed hearing loss as a long-term complication. Conclusion: The most commonly identified S. suis infection was meningitis. Over 50% of the episodes occurred in the last 2 years and have affected pig farm workers. Further surveillance is needed in order to know its prevalence

Clinical and Epidemiological Characteristics of Streptococcus suis Infections in Catalonia, Spain

Streptococcus suis (S. suis) is a human zoonotic pathogen of occupational origin, with infection acquired through contact with live pigs or pig meat. Pig farming is one of Catalonia's biggest industries and as a result this region of Spain has one of the highest density pig populations per km 2. The aim of our study was to describe the infections caused by S. suis occurring in that area over a 9-year period. A retrospective, multi-center study was carried out by searching records from 15 hospitals in Catalonia for the period between 2010 and 2019. Over the study period altogether nine cases of S. suis infection were identified in five hospitals, with five of these cases occurring in the 2018-2019 period. The mean age of patients was 48 ± 8.9 years and all of them were males. Five patients (55.6%) worked in pig farms. The most frequent manifestation of infection was meningitis (5 cases; 55.6%) followed by septic arthritis (3 cases; 33.3%). None of the patients died at 30 days; nonetheless, 4 developed hearing loss as a long-term complication. The most commonly identified S. suis infection was meningitis. Over 50% of the episodes occurred in the last 2 years and have affected pig farm workers. Further surveillance is needed in order to know its prevalence

Insights into the interactions between maleimide derivates and GSK3β combining molecular docking and QSAR.

Many protein kinase (PK) inhibitors have been reported in recent years, but only a few have been approved for clinical use. The understanding of the available molecular information using computational tools is an alternative to contribute to this process. With this in mind, we studied the binding modes of 77 maleimide derivates inside the PK glycogen synthase kinase 3 beta (GSK3β) using docking experiments. We found that the orientations that these compounds adopt inside GSK3β binding site prioritize the formation of hydrogen bond (HB) interactions between the maleimide group and the residues at the hinge region (residues Val135 and Asp133), and adopt propeller-like conformations (where the maleimide is the propeller axis and the heterocyclic substituents are two slanted blades). In addition, quantitative structure-activity relationship (QSAR) models using CoMSIA methodology were constructed to explain the trend of the GSK3β inhibitory activities for the studied compounds. We found a model to explain the structure-activity relationship of non-cyclic maleimide (NCM) derivatives (54 compounds). The best CoMSIA model (training set included 44 compounds) included steric, hydrophobic, and HB donor fields and had a good Q(2) value of 0.539. It also predicted adequately the most active compounds contained in the test set. Furthermore, the analysis of the plots of the steric CoMSIA field describes the elements involved in the differential potency of the inhibitors that can be considered for the selection of suitable inhibitors

Antifeedant and insecticidal activity of Polygonum persicaria extracts on Nomophila indistinctalis

Context: Vegetal extracts represent an alternative to control against agricultural pests that have become resistant to pesticides. Using natural products is considered to be more friendly to the environment and safe. Aims: To determine the insecticidal and antifeedant activity of Polygonum persicaria extracts of two differents populations in Chile (Valparaiso and Curico) against Nomophila indistinctalis larvae. Methods: Insecticide Resistance Action Committee (IRAC) susceptibility test was used to evaluate the insecticidal activity of the extracts at concentrations of 100, 250, 500 and 1000 mg/L; against first instar larvae of Nomophila indistinctalis. The antifeedant activity was evaluated to determine the percentage of consumption in third instar larvae on treatment. Results: When comparing the control and the treatment groups in the antifeedant activity assay, significant differences (p<0.05) were observed after 90 minutes of exposure. With respect to the insecticidal activity, all extracts showed significant effects at the applied concentrations compared to the negative control. Moreover, the dichloromethane extracts of Curico and Valparaiso at concentrations greater than 500 mg/L showed a similar insecticidal activity as compared to the commercial formulation Neem. Conclusions: This work presents for the first time the results of the anti-feeding and insecticide activity of ethanol, methanol, and dichloromethane extracts from Polygonum persicaria on Nomophila indistinctalis. The results show that the extracts of this species can be used as an alternative for biological control. In addition, the results obtained allow a bioguided fractionation for the identification of secondary metabolites present in these extracts

Analysis of the propeller conformations of the docked maleimides.

<p>(A) Scheme of the propeller conformations. (B, C) Two views of the propeller conformations of MCMs. (D) Solvent-exposed substituents (at the left) and substituents near the DFG Asp200 (at the right) of NCMs showing the presence of indol-3-yl and benzofuran-3-yl groups at each position. (E) Dihedral angles Angle1 C4’-C3′-C3-C4 (close circles to the left) and Angle2 C4″-C3″-C4-C5 (open circles to the right) for each compound series (consider labels of the atoms as represented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102212#pone-0102212-g003" target="_blank">Figure 3A</a>). The same dihedral angles are represented for the crystallographic structure of <b>4e</b> (close and open squares, PDB code: 2OW3). The dashed lines box encloses the propeller conformations.</p

CoMSIA results using the best field combinations.^a

a<p>NC is the number of components from the PLS analysis; <i>R</i>² is the square of the correlation coefficient; <i>S</i> is the standard deviation of the regression; <i>F</i> is the Fischer ratio; and <i>Q</i>² and <i>S</i>_cv are the correlation coefficient and standard deviation, respectively, of the leave-one-out (LOO) cross-validation.</p

Experimental and predicted GSK3β inhibitory activities (log(10³/IC₅₀)) of MCMs and NCMs using model CoMSIA-NCM-SHD.

a<p>Compounds <b>1</b> from reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102212#pone.0102212-Kuo1" target="_blank">[17]</a>, compounds <b>2a–2u</b> from reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102212#pone.0102212-Kozikowski1" target="_blank">[19]</a>, compounds <b>2v</b>–<b>2ba</b> and <b>5</b> from reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102212#pone.0102212-Gaisina1" target="_blank">[21]</a>, compounds <b>3</b> from reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102212#pone.0102212-Zhang2" target="_blank">[20]</a>, and compounds <b>4</b> from reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102212#pone.0102212-Zhang1" target="_blank">[18]</a>.</p>b<p>Predictions using model CoMSIA-NCM-SHD.</p>c<p>Compounds predicted in the test set.</p