Cu@PtRu Core–Shell Nanostructured Electrocatalysts Anchored on Reduced Graphene Oxide toward Methanol Oxidation

This work reports the influence of a reduced graphene oxide (rGO) support on the catalytic performance of Cu@PtRu/rGO electrocatalysts toward methanol oxidation in an acidic medium. These electrocatalysts are synthesized via a two-step reduction method; the first step utilizes ethylene glycol for the reduction of Cu2+ ions, forming Cu/rGO. In the second step, spontaneous redox reactions take place, in a process known as galvanic displacement, where the Pt2+ and Ru3+ species are reduced to form PtRu layers, and the copper is partially oxidized to the solution. Then, the Cu@PtRu/rGO core–shell is produced, comprising Cu in the inner structure (core) and PtRu on the outer part (shell). To compare the catalytic performance of the prepared nanocatalysts (NCs), Pt/C, PtRu/C, and Cu@PtRu/C are also synthesized on Vulcan XC-72R carbon. All catalysts are characterized via X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). Cyclic voltammetry (CV) and chronoamperometry (CA) are employed to measure the electrochemical performance. The core–shell/rGO combination is superior in catalytic activity to the traditional Pt/C, PtRu/C, and Cu@PtRu/C catalysts for the methanol oxidation reaction. These results suggest that Cu@PtRu/rGO exhibits a high bulk activity for methanol electrooxidation, a high stability, and a high tolerance to CO poisoning, meaning it is possible to reduce the platinum loading in proton-exchange membrane fuel cells (PEMFCs)

A study of neolignan compounds with biological activity against Paracoccidioides brasiliensis by using quantum chemical and chemometric methods

Chemometric (statistical) methods are employed to classify a set of neolignan compounds with activity against Paracoccidioides brasiliensis. The AM1 (Austin Model 1) method was used to calculate a set of molecular descriptors (properties) of the neolignan compounds under study. The descriptors were further analyzed using Principal Components Analysis (PCA), Hierarchical Cluster Analysis (HCA) and K-Nearest Neighbor (KNN) chemometric methods. The PCA and HCA methods were quite efficient to classify the compounds into two groups (active and inactive) and three descriptors were found to be important in the classification: the highest occupied molecular orbital energy (EHOMO), the bond order between C1'-R7 atoms (L14) and the bond order between C5' -R6 atoms (L22). The three variables responsible for the separation between active and inactive compounds are all electronic descriptors, therefore we can conclude that electronic effects should have an important role when one is trying to understand the activity of neolignan compounds against Paracoccidioides brasiliensis.Métodos quimiométricos (estatísticos) são empregados para classificar um conjunto de compostos derivados de neolignanas com atividade biológica contra a Paracoccidioides brasiliensis. O método AM1 (Austin Model 1) foi utilizado para calcular um conjunto de descritores moleculares (propriedades) para os compostos em estudo. A seguir, os descritores foram analisados utilizando os seguintes métodos de reconhecimento de padrões: Análise de Componentes Principais (PCA), Análise Hierárquica de Agrupamentos (HCA) e o método de K-vizinhos mais próximos (KNN). Os métodos PCA e HCA mostraram-se bastante eficientes para classificação dos compostos estudados em dois grupos (ativos e inativos). Três descritores moleculares foram responsáveis pela separação entre os compostos ativos e inativos: energia do orbital molecular mais alto ocupado (EHOMO), ordem de ligação entre os átomos C1'-R7 (L14) e ordem de ligação entre os átomos C5'-R6 (L22). Como as variáveis responsáveis pela separação entre compostos ativos e inativos são descritores eletrônicos, conclui-se que efeitos eletrônicos podem desempenhar um importante papel na interação entre receptor biológico e compostos derivados de neolignanas com atividade contra a Paracoccidioides brasiliensis

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

Tyrosinases belong to the functional copper-containing proteins family, and their structure contains two copper atoms, in the active site, which are coordinated by three histidine residues. The biosynthesis of melanin in melanocytes has two stages depending on the actions of the natural substrates L-DOPA and L-tyrosine. The dysregulation of tyrosinase is involved in skin cancer initiation. In the present study, using molecular modeling tools, we analyzed the inhibition activity of tyrosinase activity using kojic acid (KA) derivatives designed from aromatic aldehydes and malononitrile. All derivatives showed conformational affinity to the enzyme active site, and a favorable distance to chelate the copper ion, which is essential for enzyme function. Molecular dynamics simulations revealed that the derivatives formed promising complexes, presenting stable conformations with deviations between 0.2 and 0.35 Å. In addition, the investigated KA derivatives showed favorable binding free energies. The most stable KA derivatives showed the following binding free energies: −17.65 kcal mol−1 (D6), −18.07 kcal mol−1 (D2), −18.13 (D5) kcal mol−1, and −10.31 kcal mol−1 (D4). Our results suggest that these derivatives could be potent competitive inhibitors of the natural substrates of L-DOPA (−12.84 kcal mol−1) and L-tyrosine (−9.04 kcal mol−1) in melanogenesis

Analysis of kojic acid derivatives as competitive inhibitors of tyrosinase: a molecular modeling approach

This research received financial support of CAPES and CNPq.Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Modelagem Molecular. Belém, PA, Brasil / Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Planejamento e Desenvolvimento de Fármacos. Belém, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Sistemas Moleculares Complexos. Belém, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Planejamento e Desenvolvimento de Fármacos. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Planejamento e Desenvolvimento de Fármacos. Belém, PA, Brasil / Universidade Federal do Oeste do Pará. Instituto de Biodiversidade. Santarém, PA, BrasilUniversidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Modelagem Molecular. Belém, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Planejamento e Desenvolvimento de Fármacos. Belém, PA, Brasil.Abstract: Tyrosinases belong to the functional copper-containing proteins family, and their structure contains two copper atoms, in the active site, which are coordinated by three histidine residues. The biosynthesis of melanin in melanocytes has two stages depending on the actions of the natural substrates L-DOPA and L-tyrosine. The dysregulation of tyrosinase is involved in skin cancer initiation. In the present study, using molecular modeling tools, we analyzed the inhibition activity of tyrosinase activity using kojic acid (KA) derivatives designed from aromatic aldehydes and malononitrile. All derivatives showed conformational affinity to the enzyme active site, and a favorable distance to chelate the copper ion, which is essential for enzyme function. Molecular dynamics simulations revealed that the derivatives formed promising complexes, presenting stable conformations with deviations between 0.2 and 0.35 Å. In addition, the investigated KA derivatives showed favorable binding free energies. The most stable KA derivatives showed the following binding free energies: −17.65 kcal mol−1 (D6), −18.07 kcal mol−1 (D2), −18.13 (D5) kcal mol−1, and −10.31 kcal mol−1 (D4). Our results suggest that these derivatives could be potent competitive inhibitors of the natural substrates of L-DOPA (−12.84 kcal mol−1) and L-tyrosine (−9.04 kcal mol−1) in melanogenesi

Study of Genotoxicity, Activities on Caspase 8 and on the Stabilization of the Topoisomerase Complex of Isoeleutherin and Analogues

This study evaluated the genotoxicity of Ethanol Extract (EEEp), Dichloromethane Fraction (FDCMEp) and isoeleutherin isolated from Eleutherine plicata, using the micronucleus test and the impact of structural alterations on toxicity and molecular docking (topoisomerase II and DNA complex). The extract was obtained by maceration and fractionation in a chromatography column. The genotoxicity was evaluated by the micronucleus test in human hepatoma cells (HepG2). Isoeleutherin was the starting molecule in the search for analogues by structural similarity, using the ZINC and e-Molecules databases. Isoeleutherin and analogues were subjected to in silico toxicity prediction, and compounds free of toxicological risks (CP13, CP14, CP17 and isoeleutherin) were selected for molecular docking in Topoisomerase II (PDB: 1ZXM). In the micronucleus test, isoeleutherin was less genotoxic. Among the 22 isoeleutherin analogues there were variations in the toxicity profile. Molecular docking studies showed that the compounds have good complementarity in the active site with important hydrogens bonds. Therefore, the structural changes of isoeleutherin led to the obtaining of a molecule with a lower mutagenic potential, and the CP13 can be considered a prototype compound for the development of new molecules with pharmacological potential

Study of Genotoxicity, Activities on Caspase 8 and on the Stabilization of the Topoisomerase Complex of Isoeleutherin and Analogues

This study evaluated the genotoxicity of Ethanol Extract (EEEp), Dichloromethane Fraction (FDCMEp) and isoeleutherin isolated from Eleutherine plicata, using the micronucleus test and the impact of structural alterations on toxicity and molecular docking (topoisomerase II and DNA complex). The extract was obtained by maceration and fractionation in a chromatography column. The genotoxicity was evaluated by the micronucleus test in human hepatoma cells (HepG2). Isoeleutherin was the starting molecule in the search for analogues by structural similarity, using the ZINC and e-Molecules databases. Isoeleutherin and analogues were subjected to in silico toxicity prediction, and compounds free of toxicological risks (CP13, CP14, CP17 and isoeleutherin) were selected for molecular docking in Topoisomerase II (PDB: 1ZXM). In the micronucleus test, isoeleutherin was less genotoxic. Among the 22 isoeleutherin analogues there were variations in the toxicity profile. Molecular docking studies showed that the compounds have good complementarity in the active site with important hydrogens bonds. Therefore, the structural changes of isoeleutherin led to the obtaining of a molecule with a lower mutagenic potential, and the CP13 can be considered a prototype compound for the development of new molecules with pharmacological potential

(-)-5-Demethoxygrandisin B a New Lignan from <i>Virola surinamensis (Rol.) Warb.</i> Leaves: Evaluation of the Leishmanicidal Activity by In Vitro and In Silico Approaches

Leishmaniasis is a complex disease caused by infection with different Leishmania parasites. The number of medications used for its treatment is still limited and the discovery of new drugs is a valuable approach. In this context, here we describe the in vitro leishmanicidal activity and the in silico interaction between trypanothione reductase (TryR) and (-)-5-demethoxygrandisin B from the leaves of Virola surinamensis (Rol.) Warb. The compound (-)-5-demethoxygrandisin B was isolated from V. surinamensis leaves, a plant found in the Brazilian Amazon, and it was characterized as (7R,8S,7′R,8′S)-3,4,5,3′,4′-pentamethoxy-7,7′-epoxylignan. In vitro antileishmanial activity was examined against Leishmania amazonensis, covering both promastigote and intracellular amastigote phases. Cytotoxicity and nitrite production were gauged using BALB/c peritoneal macrophages. Moreover, transmission electron microscopy was applied to probe ultrastructural alterations, and flow cytometry assessed the shifts in the mitochondrial membrane potential. In silico methods such as molecular docking and molecular dynamics assessed the interaction between the most stable configuration of (-)-5-demethoxygrandisin B and TryR from L. infantum (PDB ID 2JK6). As a result, the (-)-5-demethoxygrandisin B was active against promastigote (IC50 7.0 µM) and intracellular amastigote (IC50 26.04 µM) forms of L. amazonensis, with acceptable selectivity indexes. (-)-5-demethoxygrandisin B caused ultrastructural changes in promastigotes, including mitochondrial swelling, altered kDNA patterns, vacuoles, vesicular structures, autophagosomes, and enlarged flagellar pockets. It reduced the mitochondria membrane potential and formed bonds with important residues in the TryR enzyme. The molecular dynamics simulations showed stability and favorable interaction with TryR. The compound targets L. amazonensis mitochondria via TryR enzyme inhibition