Docking Studies on Novel Analogues of 8-Chloro-Quinolones against Staphylococcus aureus

Molecular docking studies have been carried out for a better understanding of the drug-receptor interactions. All the synthesized compounds have been subjected to molecular docking against targets that have been chosen based on the specific mechanism of action of the quinolones used in the antibacterial activity screening. A study of the characteristics and molecular properties of the small molecule known as ligand has been realized. In the first stage of the study, the 2D and 3D structures have been generated. The most stable conformer for each structure was obtained by geometry optimization and energy minimization. A series of topological, conformational characteristics and QSAR properties, important to assess the flexibility and the ability of the studied conformer to bind to the protein receptor, were determined and analyzed. These properties were discussed in order to assess the flexibility and the binding ability of studied conformers to bind to the receptor protein. The docking studies have been carried out. The score and hydrogen bonds formed with the amino acids from group interaction atoms are used to predict the binding modes, the binding affinities and the orientation of the docked quinolones in the active site of the protein receptor

Molecular Descriptors and Properties of Organic Molecules

The main goal of this chapter is to reveal the importance of molecular structure analysis with specific computational tools using quantum chemistry methods based on density functional theory (DFT) with focus on pharmaceutical compounds. A wide series of molecular properties and descriptors related with chemical reactivity is discussed and compared for small organic molecules (e.g., quinolones, oxazolidinones). Structural and physicochemical information, important for quantitative structure-property relationships (QSPR) and quantitative structure-activity relationships (QSAR) modeling analysis, obtained using Spartan 14 software Wavefunction, are reported. Thus, by a computational procedure including energy minimization and predictive calculations, values of quantum chemical parameters and molecular properties related with electronic charge distribution are reported and discussed. Frontier molecular orbitals energy diagram and their bandgap provide indications about chemical reactivity and kinetic stability of the molecules. Derived parameters (ionization potential (I), electron affinity (A), electronegativity (χ), global hardness (η), softness (σ), chemical potential (μ) and global electrophilicity index (ω)) are given. Also, graphic quantities are reported: electrostatic potential maps, local ionization potential maps and LUMO maps, as visual representation of the chemically active sites and comparative reactivity of different constitutive atoms

ENTRE O REAL E O FICCIONAL: TRAÇOS AUTOBIOGRÁFICOS EM MARÍLIA DE DIRCEU

Desde a sua chegada no Brasil, o Arcadismo desempenhou um papel fundamental em nosso país, não apenas por preconizar a construção de um cânone literário com elementos propriamente nacionais, mas também por protagonizar um dos períodos mais conturbados de nossa história, conhecido pelo nome de “Inconfidência Mineira”. Uma das obras literárias que por vezes é tomada como um documento histórico, é o conjunto de liras “Marília de Dirceu”, que teve sua autoria atribuída ao luso/brasileiro Tomás Antônio Gonzaga, poeta que desde o início da conspiração manteve estreitos laços com os mentores dessa conjuração. Sabendo que tal obra poética oscila entre o factual e a subjetividade, nosso trabalho terá como objetivo analisar as características de uma possível escrita autobiográfica presente em seus versos, destacando o momento histórico e literário em que estava inserido, assim como as similitudes de Gonzaga e Maria Dorotéia entre seus respectivos personagens, Dirceu e Marília. Também evidenciaremos alguns elos que unem o mundo real com o ficcional da obra (diegese), estabelecendo uma comparação entre eles, com o intuito de aproximarmos suas peculiaridades

DO ARCADISMO AO ROMANTISMO: SIMILITUDES E ESPECIFICIDADES NA CONSTRUÇÃO DO CÂNONE NACIONAL

A lot is being discussed about the characteristics of the Brazilian’s literary esthetics of Arcadianism and Romanticism among the studies that aim to compare these literary periods, observing their factors in the creation of a canon specifically stated as national in Brazil. Issues like the nationalism, the nature and the cult to aborigine are recurrent seen in both esthetics, which usually want to recreate the aspects of an idealized Brazil, yet under the yoke of the colonialism and the monarchism. Therefore, the present study has as its main objective establishing comparative connections between both literary movements here previously mentioned, considering their historical periods and the specific relevancies of each one to our literature. For this purpose, it will be utilized the researches elaborated by Guilhermino César, described in his work Historiadores e Críticos do Romantismo, as well as the considerations made by Alfredo Bosi in his book História Concisa da Literatura Brasileira. It will also be used many essays of the researcher Ricardo Leão, present in the work Os Atenienses e a Invenção do Cânone Nacional. It will also be highlighted the contributions of Afrânio Coutinho, with the interpretation of Caminhos do Pensamento Crítico and of Antônio Candido with his essay Na Sala de Aula. Finally, anchorage will be searched in the theories of comparative literature, proposed by Sandra Nitrini in Literatura Comparada: História, Teoria e Crítica. It will be evinced, from these readings, how the Arcadianism and the Romanticism collaborate to the construction of a literature called “Brazilian”, aiming to highlight the importance that both had so that Brazil could be independent from Portugal not only in the policy issues but also in what refers to the literature produced in our country in that time.  Muito se tem discutido acerca das características das estéticas literárias brasileiras do Arcadismo e do Romantismo dentre os estudos que visam comparar tais períodos literários, observando seus fatores na criação de um cânone especificamente dito como nacional no Brasil. Temas como o nacionalismo, a natureza e o culto ao aborígene são recorrentes em ambas as estéticas, que buscam quase sempre recriar aspectos de um Brasil idealizado, ainda sob o jugo do colonialismo e do monarquismo. Assim, o presente trabalho tem por objetivo estabelecer elos comparativos entre os dois movimentos literários aqui mencionados, levando em conta seus períodos históricos e relevâncias específicas de cada um para nossa literatura. Para tanto, utilizaremos as pesquisas elaboradas por Guilhermino Cesar, descritas em sua obra Historiadores e Críticos do Romantismo, assim como as considerações feitas por Alfredo Bosi em seu livro História Concisa da Literatura Brasileira. Também lançaremos mão de diversos ensaios do pesquisador Ricardo Leão, presentes na obra Os Atenienses e a Invenção do Cânone Nacional. Destacaremos, ainda, as contribuições de Afrânio Coutinho, com a leitura de Caminhos do Pensamento Crítico e de Antônio Candido com seu ensaio Na Sala de Aula. Por fim, buscaremos ancoragem nas teorias da Literatura Comparada, propostas por Sandra Nitrini em Literatura Comparada: História, Teoria e Crítica. Evidenciaremos, a partir dessas leituras, como o Arcadismo e o Romantismo colaboraram para a construção de uma literatura chamada de “brasileira”, procurando ressaltar a importância que ambos tiveram para que o Brasil pudesse ser independente de Portugal não apenas nas questões políticas mas também no que se refere à literatura produzida em nosso país daquela época.&nbsp

Relationship between structure and molecular interactions in monolayers of specially designed aminolipids

Artificial cationic lipids are already recognized as highly efficient gene therapy tools. Here, we focus on another potential use of aminolipids, in their electrically-uncharged state, for the formation of covalently cross-linked, one-molecule-thin films at interfaces. Such films are envisioned for future (bio-)materials applications. To this end, Langmuir monolayers of structurally different aminolipids are comprehensively characterized with the help of highly sensitive surface characterization techniques. Pressure-area isotherms, Brewster angle microscopy, grazing-incidence x-ray diffraction and infrared reflection–absorption spectrometry experiments provide a detailed, comparative molecular picture of the formed monolayers. This physico-chemical study highlights the relationship between chemical structures and intermolecular interactions, which can serve as a basis for the rational design of cross-linked thin films with precisely controlled properties

<em>In Silico</em> Drug Design and Molecular Docking Studies of Some Quinolone Compound

Quinolones are an important class of heterocyclic compounds that possess interesting biological activities like antimicrobial, antitubercular, and antitumor. The objective of this study is to evaluate in silico the antitumoral and antimycobacterial activity of some quinolone derivatives by using CLC Drug Discovery Workbench Software. Docking studies were carried out for all ligands, and the docking scores were compared with the scores of standard drugs, topotecan and levofloxacin. The docking studies have been carried out to predict the most possible type of interaction, the binding affinities, and the orientations of the docked ligands at the active site of the target protein

A Comparative Structural Study in Monolayers of GPI Fragments and Their Binary Mixtures

Glycosylphosphatidylinositols (GPIs), natural complex glycolipids essential for a range of biological functions, are poorly understood with regard to their interactions and arrangements in cellular membranes. To evaluate the role of the head group in the structure formation in 2D model membranes (monolayers formed at the soft air/liquid interface), we employed the highly surface sensitive grazing incidence X-ray diffraction technique to investigate three GPI-fragments bearing the same hydrophobic part but different head groups. Condensed monolayers of simple GPI fragments are defined only by ordered alkyl chains. The monolayers of more complex fragments are additionally characterized by highly ordered head groups. Due to the strong H-bond network formed by the head groups, GPI-fragment 3 both segregates and induces order into a model membrane phospholipid (POPC) that mimics the liquid-disordered phase of cell membranes. Here, we show that the strong van der Waals interactions between hydrophobic chains overcome the head group interactions and dominate the structure formation in mixtures of GPI-fragment 3 with lipids that form liquid-condensed phases. This behaviour can be linked to the GPIs affinity for the lipid rafts

Rigid urea and self-healing thiourea ethanolamine monolayers

A series of long-tail alkyl ethanolamine analogs containing amide-, urea-, and thiourea moieties was synthesized and the behavior of the corresponding monolayers was assessed on the Langmuir–Pockels trough combined with grazing incidence X-ray diffraction experiments and complemented by computer simulations. All compounds form stable monolayers at the soft air/water interface. The phase behavior is dominated by strong intermolecular headgroup hydrogen bond networks. While the amide analog forms well-defined monolayer structures, the stronger hydrogen bonds in the urea analogs lead to the formation of small three-dimensional crystallites already during spreading due to concentration fluctuations. The hydrogen bonds in the thiourea case form a two-dimensional network, which ruptures temporarily during compression and is recovered in a self-healing process, while in the urea clusters the hydrogen bonds form a more planar framework with gliding planes keeping the structure intact during compression. Because the thiourea analogs are able to self-heal after rupture, such compounds could have interesting properties as tight, ordered, and self-healing monolayers