In Vitro and In Silico Study of the α-Glucosidase and Lipase Inhibitory Activities of Chemical Constituents from Piper cumanense (Piperaceae) and Synthetic Analogs.

Digestive enzymes are currently considered important therapeutic targets for the treatment of obesity and some associated metabolic diseases, such as type 2 diabetes. Piper cumanense is a species characterized by the presence of bioactive constituents, particularly prenylated benzoic acid derivatives. In this study, the inhibitory potential of chemical constituents from P. cumanense and some synthesized compounds was determined on digestive enzymes (pancreatic lipase (PL) and α-glucosidase (AG)). The methodology included isolating and identifying secondary metabolites from P. cumanense, synthesizing some analogs, and a molecular docking study. The chemical study allowed the isolation of four prenylated benzoic acid derivatives (1-4). Four analogs (5-8) were synthesized. Seven compounds were found to significantly inhibit the catalytic activity of PL with IC50 values between 28.32 and 55.8 µM. On the other hand, only two compounds (6 and 7) were active as inhibitors of AG with IC50 values lower than 155 µM, standing out as the potential multitarget of these chromane compounds. Enzyme kinetics and molecular docking studies showed that the bioactive compounds mainly interact with amino acids other than those of the catalytic site in both PL and AG. This work constitutes the first report on the antidiabetic and antiobesity potential of substances derived from P. cumanense.

Multitarget Action of Xanthones from Garcinia mangostana against α-Amylase, α-Glucosidase and Pancreatic Lipase.

Digestive enzymes such α-amylase (AA), α-glucosidase (AG) and pancreatic lipase (PL), play an important role in the metabolism of carbohydrates and lipids, being attractive therapeutic targets for the treatment of type 2 diabetes and obesity. Garcinia mangostana is an interesting species because there have been identified xanthones with the potential to inhibit these enzymes. In this study, the multitarget inhibitory potential of xanthones from G. mangostana against AA, AG and PL was assessed. The methodology included the isolation and identification of bioactive xanthones, the synthesis of some derivatives and a molecular docking study. The chemical study allowed the isolation of five xanthones (1-5). Six derivatives (6-11) were synthesized from the major compound, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle. Compounds with multitarget activity correspond to 2, 4, 5, 6 and 9, highlighting 6 with IC50 values of 33.3 µM on AA, 69.2 µM on AG and 164.4 µM on PL. Enzymatic kinetics and molecular docking studies showed that the bioactive xanthones are mainly competitive inhibitors on AA, mixed inhibitors on AG and non-competitive inhibitors on PL. The molecular coupling study established that the presence of methoxy, hydroxyl and carbonyl groups are important in the activity and interaction of polyfunctional xanthones, highlighting their importance depending on the mode of inhibition.

Fumigant toxicity and biochemical effects of selected essential oils toward the red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae).

Tribolium castaneum Herbst (Coleoptera: Tenebrionidae) is an insect popularly known as the red flour beetle, it is widely distributed worldwide and can cause serious damage to stored grains. Chemical control is the most used method for managing this pest, however, some substances are toxic to mammals and the environment. Therefore, the development of new effective and safe insecticides is necessary. Essential oils (EOs) can be considered as a potential alternative in the development of pesticides due to their physicochemical properties and varied effects against insects. In the current study, was determined the fumigant toxicity and biochemical effects of selected essential oils against T. castaneum. The 23 selected EOs were characterized by GC-MS and their fumigant lethal concentrations were determined. An exploratory Cluster analysis was performed to find a relationship between fumigant toxicity and chemical composition. Finally, the inhibition of the catalytic activity of acetylcholinesterase (AChE), glutathione S-transferase (GST) and catalase (CAT) was evaluated using protein homogenates obtained from T. castaneum. The results indicated that EOs with the highest fumigant potential were those with greater diversity in their composition, while the least active EOs presented mainly monoterpenes. The most active EOs were those obtained from Foeniculum vulgare and Zanthoxylum monophyllum with LC50 values of 16.23 and 18.54 µL/L air respectively. Regarding the inhibition of the enzymatic activity of the 23 EOs evaluated at 500 µL/L, only two caused an inhibition greater that 50% on AChE, which corresponded to EOs from Piper nigrum and Rosmarinus officinalis. Likewise, EOs from C. sinensis, Piper aduncum and Zanthoxylum monophyllum were the only ones able to inhibiting GST activity by more than 50%. Respecting CAT inhibition, 7 EOs caused and inhibition greater than 50%, highlighting those from Lavandula angustifolia, C. sempervirens and Eucalyptus sp. These results show that the EOs evaluated in this study seems to be a promising bio-controller of T. castaneum since have high fumigant toxicity and exert different mechanisms of action.

Effects of Essential Oils from 24 Plant Species on Sitophilus zeamais Motsch (Coleoptera, Curculionidae).

Chemical control of the maize weevil (Sitophilus zeamais) has been ineffective and presents serious collateral damage. Among plant-derived insecticides, essential oils (EOs) are suitable candidates to control this stored products pest. In this work, the insecticidal activities of 45 natural EOs against S. zeamais adults were screened, and the most promising ones (24 EOs) were characterized by GC-MS. The repellent and toxic effects (contact and fumigant) of these 24 EOs were determined, and by a cluster analysis they were classified into two groups considering its fumigant activity and contact toxicity. For the EOs with the highest fumigant potential (14 oils) and their main active constituents (17 compounds), lethal concentrations were determined. The most active EOs were those obtained from L. stoechas and L. alba, with LC50 values of 303.4 and 254.1 µL/L air and characterized by a high content of monoterpenes. Regarding the major compounds, the oxygenated monoterpenes R-(+)-pulegone (LC50 = 0.580 mg/L air), S-(-)-pulegone (LC50 = 0.971 mg/L air) and R-(-)-carvone (LC50 = 1.423 mg/L air) were the most active, as few variations in their concentrations significantly increased insect mortality.

Antifungal Activity of Chemical Constituents from Piper pesaresanum C. DC. and Derivatives against Phytopathogen Fungi of Cocoa.

In this study, the antifungal potential of chemical constituents from Piper pesaresanum and some synthesized derivatives was determined against three phytopathogenic fungi associated with the cocoa crop. The methodology included the phytochemical study on the aerial part of P. pesaresanum, the synthesis of some derivatives and the evaluation of the antifungal activity against the fungi Moniliophthora roreri, Fusarium solani and Phytophthora sp. The chemical study allowed the isolation of three benzoic acid derivatives (1-3), one dihydrochalcone (4) and a mixture of sterols (5-7). Seven derivatives (8-14) were synthesized from the main constituents, of which compounds 9, 10, 12 and 14 are reported for the first time. Benzoic acid derivatives showed strong antifungal activity against M. roreri, of which 11 (3.0 ± 0.8 µM) was the most active compound with an IC50 lower compared with positive control Mancozeb® (4.9 ± 0.4 µM). Dihydrochalcones and acid derivatives were active against F. solani and Phytophthora sp., of which 3 (32.5 ± 3.3 µM) and 4 (26.7 ± 5.3 µM) were the most active compounds, respectively. The preliminary structure-activity relationship allowed us to establish that prenylated chains and the carboxyl group are important in the antifungal activity of benzoic acid derivatives. Likewise, a positive influence of the carbonyl group on the antifungal activity for dihydrochalcones was deduced.

Structure and photophysics of indigoids for singlet fission: Cibalackrot.

We report an investigation of structure and photophysics of thin layers of cibalackrot, a sturdy dye derived from indigo by double annulation at the central double bond. Evaporated layers contain up to three phases, two crystalline and one amorphous. Relative amounts of all three have been determined by a combination of X-ray diffraction and FT-IR reflectance spectroscopy. Initially, excited singlet state rapidly produces a high yield of a transient intermediate whose spectral properties are compatible with charge-transfer nature. This intermediate more slowly converts to a significant yield of triplet, which, however, does not exceed 100% and may well be produced by intersystem crossing rather than singlet fission. The yields were determined by transient absorption spectroscopy and corrected for effects of partial sample alignment by a simple generally applicable procedure. Formation of excimers was also observed. In order to obtain guidance for improving molecular packing by a minor structural modification, calculations by a simplified frontier orbital method were used to find all local maxima of singlet fission rate as a function of geometry of a molecular pair. The method was tested at 48 maxima by comparison with the ab initio Frenkel-Davydov exciton model.

Cinerin C: a macrophyllin-type bicyclo[3.2.1]octane neolignan from Pleurothyrium cinereum (Lauraceae).

The structure of naturally-occurring cinerin C [systematic name: (7S,8R,3'R,4'S,5'R)-Δ(8')-4'-hydroxy-5,5',3'-trimethoxy-3,4-methylenedioxy-2',3',4',5'-tetrahydro-2'-oxo-7.3',8.5'-neolignan], isolated from the ethanol extract of leaves of Pleurothyrium cinereum (Lauraceae), has previously been established by NMR and HRMS spectroscopy, and its absolute configuration established by circular dichroism measurements. For the first time, its crystal structure has now been established by single-crystal X-ray analysis, as the monohydrate, C(22)H(26)O(7)·H(2)O. The bicyclooctane moiety comprises fused cyclopentane and cyclohexenone rings which are almost coplanar. An intermolecular O-H···O hydrogen bond links the 4'-OH and 5'-OCH(3) groups along the c axis.

In vitro anti-inflammatory effects of naturally-occurring compounds from two Lauraceae plants

The in vitro anti-inflammatory effects of seven known lignans and one dihydrochalcone isolated from the leaves of two Lauraceae species (Pleurothyrium cinereum and Ocotea macrophylla), were evaluated through the inhibition of COX-1, COX-2, 5-LOX and the aggregation of rabbit platelets induced by PAF, AA and ADP. (+)-de-4"-O--methylmagnolin 4 was found to be a potent COX-2/5-LOX dual inhibitor and PAF-antagonist (COX-2 IC50 2.27 µM; 5-LOX IC50 5.05 µM; PAF IC50 2.51 µM). However, all compounds exhibited an activity at different levels, indicating good anti-inflammatory properties to be considered in further structural optimization studies.

Os efeitos anti-inflamatórios in vitro de sete conhecidos lignanos e uma dihidrocalcona isolados das folhas de duas espécies da família Lauraceae (Pleurothyrium cinereum e Ocotea macrophylla) foram avaliados por meio da inibição da COX1, COX-2, 5-LOX e agregação de plaquetas de coelhos induzida por PAF, AA e ADP. A (+)-4"-O-metilmagnolina-4 foi encontrada como mais potente inibidora tanto da COX-2 quanto de 5-LOX e antagonista de PAF (COX-2 IC50 2,27 µM; 5- LOX IC50 5,05 µM; PAF IC50 2,51 µM). Entretanto, todos compostos mostram uma atividade em intensidades diferentes, indicando boas propriedades anti-inflamátorias a serem consideradas para futuros estudos de modificações e otimização estruturais.

In vitro anti-inflammatory effects of naturally-occurring compounds from two Lauraceae plants.

The in vitro anti-inflammatory effects of seven known lignans and one dihydrochalcone isolated from the leaves of two Lauraceae species (Pleurothyrium cinereum and Ocotea macrophylla), were evaluated through the inhibition of COX-1, COX-2, 5-LOX and the aggregation of rabbit platelets induced by PAF, AA and ADP. (+)-de-4"-O-methylmagnolin 4 was found to be a potent COX-2/5-LOX dual inhibitor and PAF-antagonist (COX-2 IC(50) 2.27 µM; 5-LOX IC(50) 5.05 µM; PAF IC(50) 2.51 µM). However, all compounds exhibited an activity at different levels, indicating good anti-inflammatory properties to be considered in further structural optimization studies.

PAF-antagonistic bicyclo[3.2.1]octanoid neolignans from leaves of Ocotea macrophylla Kunth. (Lauraceae).

Di-nor-benzofuran neolignan aldehydes, Delta(7)-3,4-methylenedioxy-3'-methoxy-8',9'-dinor-4',7-epoxy-8,3'-neolignan-7'-aldehyde (ocophyllal A) 1, Delta(7)-3,4,5,3'-tetramethoxy-8',9'-dinor-4',7-epoxy-8,3'-neolignan-7'-aldehyde (ocophyllal B) 2, and macrophyllin-type bicyclo[3.2.1]octanoid neolignans (7R, 8R, 3'S, 4'S, 5'R)-Delta(8)'-4'-hydroxy-5'-methoxy-3,4-methylenedioxy-2',3',4',5'-tetrahydro-2'-oxo-7.3',8.5'-neolignan (ocophyllol A) 3, (7R, 8R, 3'S, 4'S, 5'R)-Delta(8)'-4'-hydroxy-3,4,5'-trimethoxy-2',3',4',5'-tetrahydro-2'-oxo-7.3',8.5'-neolignan (ocophyllol B) 4, (7R, 8R, 3'S, 4'S, 5'R)-Delta(8)'-4'-hydroxy-3,4,5,5'-tetramethoxy-2',3',4',5'-tetrahydro-2'-oxo-7.3',8.5'-neolignan (ocophyllol C) 5, as well as 2'-epi-guianin 6 and (+)-licarin B 7, were isolated and characterized from leaves of Ocotea macrophylla (Lauraceae). The structures and configuration of these compounds were determined by extensive spectroscopic analyses. Inhibition of platelet activating factor (PAF)-induced aggregation of rabbit platelets were tested with neolignans 1-7. Although compound 6 was the most potent PAF-antagonist, compounds 3-5 showed some activity.

Identificación de daños en vigas de hormigón experimentales y analíticas usando metodologías modales

En este artículo se presenta una evaluación de metodologías no destructivas para detectar defectos o daños en estructuras. Todos los métodos se basan en el uso directo o indirecto de las propiedades modales medidas en la estructura sin y con daño. En particular, se evaluó el uso de matrices definidas en términos de un número limitado de frecuencias y modos, entre ellas matrices de rigidez y flexibilidad modificadas. Se usaron dos tipos de modelos en la investigación: modelos experimentales de vigas de hormigón con y sin refuerzo longitudinal y sus correspondientes modelos analíticos creados con el programa de elementos finitos ANSYS. Se construyeron modelos sin daño para ser usados como vigas de control y modelos con una y dos grietas superficiales que atravesaban todo el ancho de la viga. Las propiedades modales de las vigas simplemente soportadas se obtuvieron usando una carga impulsiva y el método de Respuesta en Frecuencia. De ambos modelos se obtuvieron los parámetros dinámicos necesarios para calcular la diferencia entre las diversas matrices que caracterizan a las vigas con y sin grietas. Para los casos estudiados se encontró que las matrices de flexibilidad definidas con los tres primeros modos de la viga fueron los indicadores más eficientes. Además se evaluó la posibilidad de usar el cambio en las frecuencias naturales y en los modos de vibración como indicadores de daños, pero los resultados no fueron satisfactorios. (AU)

3,6-Dihydroxy-2-(11-phenylundecanoyl)cyclohex-2-en-1-one from Virola venosa bark.

The structure of the title compound, C23H32O4, an arylalkanone isolated from the petroleum ether fraction of the ethanol extract of the bark of Virola venosa, has been established by NMR spectroscopy and, for the first time, by X-ray structure analysis. Two independent molecules of the same enantiomer are present in the unit cell. Both molecules exhibit an intramolecular hydrogen bond, which can be correlated with a rare signal observed at 18.28 p.p.m. in the 1H NMR spectrum. The packing, in space group P1, is determined by a pseudo-center of symmetry leading to a short intermolecular contact, which is present in one molecule but does not occur in the other. As a consequence, the O-C-C-O torsion angles [-16.9 (3) and -12.7 (3) degrees ] through the ketone and its adjacent hydroxy group are significantly different in the two molecules.

Simulación numérica de la respuesta sísmica del sistema tridimensional acoplado edificio - rieles - contrapeso de un ascensor

Los ascensores son componentes no estructurales de edificios que muchas veces cumplen funciones de vital importancia como es el caso de aquellos localizadores en hospitales. Así como el edificio puede ser afectado por un movimiento sísmico fuerte, tambien los ascensores pueden sufrir daños. Durante el terremoto de 1971 en San Fernando, California, cientos de ascensores fueron severamente dañados en el área de Los Angeles. Esto hizo que por primera vez se incorporaran en los códigos para diseño e instalación de asensores medidas para tener en cuenta el efecto de los terremotos. Si bien los daños reportados durante terremotos subsiguientes en California disminuyeron, todavía se observaron numerosas fallas. La falla más común fue el descarrilamiento del contrapeso en los ascensores eléctricos, seguida por la deformación permanente de los rieles. Este proyecto de investigación pretende explicar el comportamiento de los contrapesos durante un terremoto fuerte mediante una simulación numérica. Se desarrollo un modelo de un edificio multipiso en donde se incluye un modelo de contrapeso y sus dos rieles. El edificio se sometio a la aceleración en la base registrada durante un terremoto histórico para obtener la respuesta en el tiempo. Los resultados confirman que, a no ser que se implementen medidas especiales, el sistema riel - contrapeso va a fallar debido al mismo. El modelo desarrollado y metodología usada para calcular la respuesta pueden ser útiles para estudiar cómo reforzar los ascensores para que resistan mejor los movimientos sísmicos ÿ(AU)

Comportamiento sísmico y rehabilitación de residencias soportadas en columnas y localizadas en terrenos escarpados

Este artículo presenta un resumen de una investigación sobre el comportamiento y rehabilitación sísmica de residencias típicas ubicadas en laderas o terrenos escarpados y apoyadas en columnas gravitatorias. El estudio, que se basa en simulaciones numéricas, considera la amplificación del movimiento sísmico debido a la topografía irregular en donde se encuentran localizadas las residencias. El mismo se enfoca en la evaluación estructural de este tipo de residencias cuyos parámetros geométricos típicos fueron obtenidos de un muestreo a través de la isla de Puerto Rico. Como métodos para evaluar la vulnerabilidad de las residencias bajo cargas sísmicas se utilizaron análisis no lineales monotónicos y dinámicos transitorios. Para los análisis no lineales dinámicos transitorios se generaron registros artificiales de terremotos sin incluir e incluyendo la amplificación topográfica. Además se desarrolló una metodología para utilizarse como indicador de colapso en las estructuras. Se propusieron dos nuevos indicadores de falla, los que fueron continuamente verificados a lo largo de la duración de los terremotos. El primero de estos indicadores se basa en el determinante de la matriz de rigidez y el segundo en el periodo fundamental de la estructura. Luego de examinar los resultados de los análisis mencionados anteriormente, se desarrolló un sistema de rehabilitación o de mejoramiento sísmico. Por último, se desarrollaron una serie de tablas de las cuales se puede obtener el sistema de rehabilitación apropiado para cada estructura de las viviendas, de acuerdo a los tamaños de sus elementos estructurales, el largo libre de sus elementos y la altura de las columnas del primer piso. Además se proveyeron recomendaciones, especificaciones y detalles estructurales, como requerimientos mínimos para una implementación confiable del sistema de rehabilitación sísmica.(AU)

Evaluación de las vibraciones del suelo causadas por trenes subterráneos usando elementos finitos

En este trabajo se presenta un análisis numérico de las vibraciones inducidas por la propagación de ondas originadas por el paso de trenea a través de túneles subterráneos. La metodología desarrollada es útil para realizar el análisis requerido por agencias reguladoras cuando los resultados de investigaciones preliminares indican que se van a exceder los umbrales seguros de vibración. Se estudiaron los niveles de vibraciones en los túneles del proyecto del Tren Urbano, que se está construyendo en San Juan, Puerto Rico. Se estudiaron secciones típicas de cada una de las tres clases de túneles que se usaron en el proyecto. El método de elementos finitos se utilizó para discretizar la geometría de los modelos y para calcular los desplazamientos, las velocidades y los esfuerzos inducidos por la propagación de ondas. El programa de elementos finitos ALGOR se utilizó para modelar el suelo, los diversos túneles y las estructuras en la superficie. Los resultados de la simulación numérica se compararon con mediciones en el campo efectuadas antes del inicio del proyecto Tren Urbano por la compañía consultora Harris Miller Miller & Harson, Inc. Se encontró que los resultados de ambos procedimientos comparan favorablemente(AU)