A New Multi-Objective Approach for Molecular Docking Based on RMSD and Binding Energy

Ligand-protein docking is an optimization problem based on predicting the position of a ligand with the lowest binding energy in the active site of the receptor. Molecular docking problems are traditionally tackled with single-objective, as well as with multi-objective approaches, to minimize the binding energy. In this paper, we propose a novel multi-objective formulation that considers: the Root Mean Square Deviation (RMSD) difference in the coordinates of ligands and the binding (intermolecular) energy, as two objectives to evaluate the quality of the ligand-protein interactions. To determine the kind of Pareto front approximations that can be obtained, we have selected a set of representative multi-objective algorithms such as NSGA-II, SMPSO, GDE3, and MOEA/D. Their performances have been assessed by applying two main quality indicators intended to measure convergence and diversity of the fronts. In addition, a comparison with LGA, a reference single-objective evolutionary algorithm for molecular docking (AutoDock) is carried out. In general, SMPSO shows the best overall results in terms of energy and RMSD (value lower than 2A for successful docking results). This new multi-objective approach shows an improvement over the ligand-protein docking predictions that could be promising in in silico docking studies to select new anticancer compounds for therapeutic targets that are multidrug resistant.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Formation of hydroxyl radicals by α-Fe2O3 microcrystals and its role in photodegradation of 2,4- dinitrophenol and lipid peroxidation

α-Fe2O3 microcrystals were produced for application as catalyst in different oxidation processes in both chemical and biological matrices. Hematite was produced by sol–gel method in situ with silica matrix and characterized by X-ray diffraction analysis, scanning electron microscopy with energy-dispersive X-ray spectrometry, and transmission electron microscopy. The ability of the catalyst to produce hydroxyl radicals (·OH) was evaluated by electron paramagnetic resonance measurements using 5,5-dimethyl- 1-pyrroline-N-oxide (DMPO) as spin trap. Characterization of the resulting DMPO-OH adduct established that α-Fe2O3 microcrystals could generate ·OH when Fenton chemistry was present. Additionally, the catalyst exhibited semiconducting properties, as the DMPO-OH signal was produced under visible-light irradiation in presence of O2 but without requiring H2O2. In a pollution control context, 2,4-dinitrophenol (2,4-DNP) degradation was used as probe reaction, with >99 % of this pollutant being removed in presence of H2O2 under visible light. NO 2 − , NO 3 − , hydroxylated compounds, and a carboxylic acid were identified as photoproducts, suggesting a degradation pathway. Finally, catalyst reactivity in biological matrices was evaluated by oxidative degradation of lipids, revealing that α-Fe2O3 is a good oxidative stress inducer, representing a new application for materials based on iron oxides.http://unidadinvestigacion.usta.edu.c

Actividad inhibitoria de ⍺-glucosidasa de tres plantas medicinales mexicanas.

En México, la diabetes mellitus tipo 2 se situó como la tercera principal causa de muerte en 2020. Una estrategia para tratar la diabetes consiste en impedir que los niveles de glucosa en sangre aumenten en pacientes sin dietas saludables. Por ello, en el presente trabajo se estudió la actividad inhibitoria de α-glucosidasa de tres especies de plantas medicinales. Los extractos orgánicos de Smilax sp. exhibieron concentraciones inhibitorias medias de α�glucosidasa menores a 0.6 μg/mL, mientras que el control positivo quercetina resultó menos potente. Esta evidencia sugiere que el uso medicinal de Smilax sp. se podría investigar mediante la inhibición de α-glucosidasa intestinal

Docking Inter/Intra-Molecular Mediante Metaheurísticas Multi-objetivo

El Acoplamiento Molecular (Molecular Docking) es un problema de optimización de gran complejidad que consiste en predecir la orientación de dos moléculas: el ligando y el receptor, de manera que formen un complejo molecular energéticamente estable. El docking molecular es un problema tradicionalmente tratado con éxito mediante metaheurísticas para la optimización de un objetivo: la mínima energía libre de unión. Sin embargo, en la literatura actual no se encuentran muchos trabajos que traten este problema desde el punto de vista multiobjetivo. En este sentido, todavía no existen estudios comparativos con el fin de dilucidar qué técnica (o qué tipo de ellas) ofrece un mejor rendimiento en general. En este estudio realizamos una comparativa experimental de una serie de algoritmos multiobjetivo representativos del estado del arte actual, para la resolución de instancias complejas de docking molecular. En concreto, los algoritmos evaluados son: NSGA-II, ssNSGA-II, SMPSO, GDE3, MOEA/D y SMS-EMOA. Para ello, hemos seguido un enfoque de optimización basado en las energías inter- e intra-molecular, siendo éstos los dos objetivos a minimizar. En la evaluación de los al- goritmos hemos aplicado métricas de rendimiento para medir la convergencia y la diversidad de los frentes de Pareto resultantes, respecto a frentes de referencia calculados. Además, en comparación con soluciones mono-objetivo obtenidas por técnicas de referencia en el problema (LGA), comprobamos cómo los algoritmos multi-objetivo evaluados son capaces de obtener conformaciones moleculares de mínima energía de acoplamiento.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF MACROALGAE COLLECTED FROM BAJA CALIFORNIA SUR, MEXICO

Objective: This study aimed to establish the anti-inflammatory potential of macroalgae from Baja California Sur, Mexico. Methods: The anti-inflammatory activity of the extracts from 10 macroalgae species was evaluated in vitro and in vivo. Dichloromethane, ethanolic, and aqueous extracts were obtained from each species. The criteria used to determine anti-inflammatory activity included 1) the membrane protection of human red blood cells (HRBCs) against hemolysis induced by hypotonicity, 2) the inhibition of heat-induced protein denaturation (IDP), and 3) the inhibition of mouse ear edema and the myeloperoxidase (MPO) enzyme. Results: The dichloromethane extracts of Gracilaria vermiculophylla and Opuntiella californica were the most active, both in vitro and in vivo. These extracts resulted in values of HRBC membrane protection above 95%, which were similar to those obtained with diclofenac sodium. And reduce the inflammation with edema inhibition percentage up to 60 % while the control indomethacin was able to inhibit edema by 82.3 %. Conclusion: The bioprospection of several macroalgae species from Bahía de La Paz, Mexico, allowed the identification of two species with promising anti-inflammatory activity. Gracilaria vermiculophylla showed interesting topical anti-inflammatory effects and a profile of compounds (flavonoids and terpenes) that may contribute to the potential biological properties of this seaweed. This study represents the first report of the anti-inflammatory potential of O. californica

Estudio de Estrategias de Archivo en PSO Multi-Objetivo para el Docking Molecular

El acoplamiento molecular es un problema de optimización complejo cuyo objetivo es la predicción de la posición de un ligando en el sitio activo de un receptor con la mínima energía de unión. Este problema puede ser formulado como un problema de optimización de dos objetivos que minimiza la energía de unión y la desviación de la media cuadrática de las posiciones atómicas (RMSD) de los ligandos. En este contexto, el algoritmo multi-objetivo de swarm-intelligence SMPSO mostró un rendimiento destacable. SMPSO se caracteriza por usar un archivo externo para almacenar las soluciones no dominadas y como base para estrategia de selección de líder. En este artículo, se analizan diferentes variantes de SMPSO basadas en diferentes estrategias de archivo utilizando un benchmark de instancias moleculares. Este estudio revela que la variante SMPSOhv obtiene los mejores resultados.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

CHEMICAL COMPOSITION AND ANTI-INFLAMMATORY ACTIVITY OF Roldana platanifolia

Recebido em 21/04/2015; aceito em 23/06/2015; publicado na web em 12/08/2015 The chemical study of Roldana platanifolia led to the isolation of b-caryophyllene, five eremophilanolides, chlorogenic acid, and a mixture of b-sitosterol-stigmasterol, b-sitosteryl glucopyranoside, and sucrose. The anti-inflammatory activities of the extracts and isolated products were tested using the 12-O-tetradecanoylphorbol-13-acetate (TPA) model of induced acute inflammation. The acetone and methanol extracts showed dose dependent activities (ID50 0.21 and 0.32 mg/ear, respectively), while none of the isolated compounds exhibited relevant edema inhibition. The active extracts were also evaluated with the myeloperoxidase assay technique (MPO) to determine their ability to prevent neutrophil infiltration. Results showed that the anti-inflammatory activity was related to the compound's ability to inhibit pro-inflammatory mediators such as neutrophils

Efecto anti-tumoral de dos triterpenos aislados de una planta medicinal

Los ácidos masticadienónico (1) y 3α-OH masticadienoico (2) son los principales metabolitos secundarios aislados de la corteza de Amphipterygium adstringens. En trabajos previos se han investigado las propiedades biológicas de estos ácidos. Inicialmente, se demostró la actividad antiinflamatoria en dos modelos de inflamación aguda, carragenina y TPA (12-O-tetradecanoilphorbol-13- acetato) (Oviedo, 2004). Por otro lado, se demostró que estos compuestos inhiben la proliferación de las líneas celulares de cáncer humano (Oviedo, 2005). Respecto al mecanismo anti-tumoral recientemente se informó el efecto de 2 sobre las funciones bioenergéticas y la permeabilidad de la membrana mitocondrial (Dalla, 2012). Sin embargo, no se ha investigado su actividad anti-tumoral in vivo. En este trabajo se investigó el efecto de 1 y 2 sobre el crecimiento tumoral en un modelo murino. Los resultados de esta investigación demuestran que los ácidos 1 y 2 tienen un efecto anti-tumoral en xenotransplantes de carcinoma prostático.The masticadienonic acid (1) and 3α-OH masticadienoic acid (2) are the main secondary metabolites of the barck from Amphipterygium adstringens (Navarrete, 2006). In previous works, were investigated the biological properties of these acids. First, was demonstrated their anti-inflamatory activity by TPA (12-Otetradecanoylphorbol- 13-acetate) and carrageenan inflammatory acute models. Also, has been demonstrated that 1 and 2 compounds inhibit the proliferation of the human cancer cell lines, HCT-15 (colon), MCF-7 (breast), U-251 (CNS), PC-3 (prostate), K-562 (leukaemia), (Oviedo, 2005). Respect to the anti-tumor mechanism recently was informed the effect of 2 on bioenergetics functions and permeability of mithocondrial membrane (Dalla, 2012). However, there are no studies about anti-tumor activity of 1 and 2 in vivo. In this work we investigated the effect of 1 and 2 on growth tumor in a murine model. The results of this research showed that acids 1 and 2 have anti-tumor effect in xenografts of prostatic carcinoma

Phenolic Compounds in Organic and Aqueous Extracts from Acacia farnesiana Pods Analyzed by ULPS-ESI-Q-oa/TOF-MS. In Vitro Antioxidant Activity and Anti-Inflammatory Response in CD-1 Mice

Abstract: Background: Acaciafarnesiana (AF) pods have been traditionally used to treat dyspepsia, diarrhea and topically for dermal inflammation. Main objectives: (1) investigate the antioxidant activity and protection against oxidative-induced damage of six extracts from AF pods and (2) their capacitytocurbtheinflammationprocessaswellastodown-regulatethepro-inflammatorymediators. Methods: Five organic extracts (chloroformic, hexanic, ketonic, methanolic, methanolic:aqueous and one aqueous extract) were obtained and analyzed by UPLC-ESI-Q-oa/TOF-MS. Antioxidant activity (DPPH•, ORAC and FRAP assays) and lipid peroxidation (TBARS assay) were performed. Assessmentofanti-inflammatorypropertieswasmadebytheearedemainducedmodelinCD-1mice andMPOactivityassay. Likewise,histologicalanalysis,IL-1β,IL-6,IL-10,TNF-α,COXmeasurements plus nitrite and immunohistochemistry analysis were carried out. Results: Methyl gallate, gallic acid,galloyl glucose isomer 1, galloyl glucose isomer 2, galloyl glucose isomer 3, digalloyl glucose isomer 1, digalloyl glucose isomer 2, digalloyl glucose isomer 3, digalloyl glucose isomer 4, hydroxytyrosol acetate, quinic acid, and caffeoylmalic acid were identified. Both organic and aqueous extracts displayed antioxidant activity. All extracts exhibited a positive effect on the interleukins, COX and immunohistochemistry assays. Conclusion: All AF pod extracts can be effective as antioxidant and topical anti-inflammatory agents. Keywords: Acacia farnesiana pods; antioxidant and anti-inflammatory activities; bioactive compounds; polyphenol

Estudio fitoquímico preliminar del extracto hidroalcohólico de hoja de Crescentia cujete L. (Totumo) y evaluación de la actividad antiinflamatoria de un gel para uso tópico

Crescentia cujete L. (Totumo), es un árbol de la familia Bignoniáceae que se encuentra distribuido ampliamente en América, el Caribe, algunos países africanos y el sur de Asia. Las cáscaras de sus frutos son de alto valor artesanal y su pulpa es la base para un fitomedicamento complementario en el tratamiento de transtornos respiratorios leves en Colombia. Algunas comunidades rurales del Caquetá, al sur de Colombia, utilizan sus hojas en modo de infusión, en el tratamiento tópico de la inflamación. En este estudio se pudo establecer por medio de un análisis fitoquímico preliminar (pruebas a la gota) la presencia de esteroides, triterpenos, saponinas, taninos, flavonoides, cumarinas, y quinonas en el extracto hidroalcohólico de hojas de C. cujete. Aunado a esto, también se pudo establecer que un gel preparado a base del extracto hidroalcohólico de hoja de C. cujete, posee una ligera actividad antiinflamatoria en modelo de edema auricular inducido con TPA, lo cual permite indicar de forma preliminar, una relación entre el uso popular que algunas comunidades rurales en Colombia hacen de esta planta como medicamento antiinflamatorio tópico y los resultados aquí obtenidos