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14 results on '"Miceli, Leonardo A."'

3. Evaluation of Biological Activities of Quinone-4-oxoquinoline Derivatives against Pathogens of Clinical Importance

Author

Juliana Martins, Francislene, primary, Savacini Sagrillo, Fernanda, additional, Josianne Vinturelle Medeiros, Rafaelle, additional, Gonçalves de Souza, Alan, additional, Rodrigues Pinto Costa, Amanda, additional, Silva Novais, Juliana, additional, Alves Miceli, Leonardo, additional, Campos, Vinícius, additional, Marie Sá Figueiredo, Agnes, additional, Claudia Cunha, Anna, additional, Lidmar von Ranke, Natalia, additional, Lamim Bello, Murilo, additional, Abrahim-Vieira, Bárbara, additional, De Souza, Alessandra, additional, Ratcliffe, Norman, additional, da Costa Santos Boechat, Fernanda, additional, Cecília Bastos Vieira de Souza, Maria, additional, Rangel Rodrigues, Carlos, additional, and Carla Castro, Helena, additional

Published
2022
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5. Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

Author

Leite, Talita Odriane Custodio, primary, Novais, Juliana Silva, additional, de Carvalho, Beatriz Lima Cosenza, additional, Ferreira, Vitor Francisco, additional, Miceli, Leonardo Alves, additional, Fraga, Letícia, additional, Abrahim-Vieira, Bárbara, additional, Rodrigues, Carlos Rangel, additional, Sá Figueiredo, Agnes Marie, additional, Castro, Helena Carla, additional, and Cunha, Anna Claudia, additional

Published
2020
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7. Synthesis, In Vitroand In SilicoStudies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

Author

Leite, Talita O. C., Novais, Juliana S., Carvalho, Beatriz Lima Cosenza de, Ferreira, Vitor Francisco, Miceli, Leonardo Alves, Fraga, Letícia, Abrahim-Vieira, Bárbara, Rodrigues, Carlos Rangel, Figueiredo, Agnes Marie Sá, Castro, Helena Carla, and Cunha, Anna Claudia

Abstract

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 μg.mL-1) and Gram-negative bacteria (MIC = 8 μg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

Published
2020
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9. Volatilidade e dinâmica da correlação da taxa de câmbio na América Latina: o caso do Brasil, Chile e México

Author

Miceli, Leonardo Francisco Lacerda, Escolas::EPGE, FGV, Bonomo, Marco Antônio Cesar, Medeiros, Marcelo C., and Fernandes, Marcelo

Subjects
Correlação dinâmica, Economia, Volatilidade, Câmbio, Taxa de câmbio
Abstract

O trabalho tem como objetivo descrever um processo de transmis são de choques na correlação da taxa de câmbio do Brasil, Chile, Euro e México com base no modelo de correlação dinâmica de [Engle, 2002]. O modelo é estendido para capturar efeitos assi métricos na volatilidade e na correlação. A trajetória estimada da correlação mostra-se com desvios significativos em relação a correla ção incondicional, a amplitude da correlação condicional é elevada e há inclusive alteração de sinal quando a correlação é feita em relação ao Euro. Num calculo de valor em risco, o modelo com correlação dinâmica tem uma performance muito superior a um modelo com correlação constante, levando-se em conta os mesmos processos de volatilidade.

Published
2008

13. Computational Studies of Benzoxazinone Derivatives as Antiviral Agents against Herpes Virus Type 1 Protease.

Author

e Mello, Juliana F. R., Botelho, Nathália C., de Souza, Alessandra M. T., de Oliveira, Riethe, de Brito, Monique A., Abrahim-Vieira, Bárbara de A., Sodero, Ana Carolina R., Castro, Helena C., Cabral, Lucio M., Miceli, Leonardo A., and Rodrigues, Carlos R.

Subjects
BENZOXAZINONES, ANTIVIRAL agents, HERPES simplex virus, BIOAVAILABILITY, MOLECULAR docking
Abstract

Herpes simplex virus infections have been described in the medical literature for centuries, yet the the drugs available nowadays for therapy are largely ineffective and low oral bioavailability plays an important role on the inefficacy of the treatments. Additionally, the details of the inhibition of Herpes Virus type 1 are still not fully understood. Studies have shown that several viruses encode one or more proteases required for the production new infectious virions. This study presents an analysis of the interactions between HSV-1 protease and benzoxazinone derivatives through a combination of structure-activity relationships, comparative modeling and molecular docking studies. The structure activity relationship results showed an important contribution of hydrophobic and polarizable groups and limitations for bulky groups in specific positions. Two Herpes Virus type 1 protease models were constructed and compared to achieve the best model which was obtained by MODELLER. Molecular docking results pointed to an important interaction between the most potent benzoxazinone derivative and Ser129, consistent with previous mechanistic data. Moreover, we also observed hydrophobic interactions that may play an important role in the stabilization of inhibitors in the active site. Finally, we performed druglikeness and drugscore studies of the most potent derivatives and the drugs currently used against Herpes virus. [ABSTRACT FROM AUTHOR]

Published
2015
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14. Structural model of haptoglobin and its complex with the anticoagulant ecotin variants: structure-activity relationship study and analysis of interactions.

Author

Sathler, Plínio Cunha, Lourenço, André Luiz, Miceli, Leonardo Alves, Rodrigues, Carlos Rangel, Albuquerque, Magaly Girão, Cabral, Lúcio Mendes, and Castro, Helena Carla

Subjects
HAPTOGLOBINS, ANTICOAGULANTS, STRUCTURE-activity relationships, ESCHERICHIA coli, IMMUNOGLOBULINS, GENETIC mutation, BINDING energy
Abstract

Recently the literature described the binding of Haptoglobin (HP) with ecotin, a fold-specific serine-proteases inhibitor with an anticoagulant profile and produced by Escherichia coli. In this work, we used some in silico and in vitro techniques to evaluate HP 3D-fold and its interaction with wild -type ecotin and two variants. Our data showed HP models conserved trypsin fold, in agreement to the in vitro immunological recognition of HP by trypsin antibodies. The analysis of the three ecotin-HP complexes using the mutants RR and TSRR/R besides the wild type revealed several hydrogen bonds between HP and ecotin secondary site. These data are in agreement with the in vitro PAGE assays that showed the HP-RR complex in native gel conditions. Interestingly, the ternary complex interactions varied depending on the inhibitor structure and site -directed mutation. The interaction of HP with TSRR/R involved new residues compared to wild type, which infers a binding energy increase caused by the mutation. [ABSTRACT FROM AUTHOR]

Published
2014
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