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Your search keyword '"Vallone, Alessandra"' showing total 2 results
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2 results on '"Vallone, Alessandra"'

1. Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside Macrophages

Author

Paolino, Marco, Brindisi, Margherita, Vallone, Alessandra, Butini, Stefania, Campiani, Giuseppe, Nannicini, Chiara, Giuliani, Germano, Anzini, Maurizio, Lamponi, Stefania, Giorgi, Gianluca, Sbardella, Diego, Ferraris, Davide M., Marini, Stefano, Coletta, Massimo, Palucci, Ivana, Minerva, Mariachiara, Delogu, Giovanni, Pepponi, Ilaria, Goletti, Delia, Cappelli, Andrea, Gemma, Sandra, Brogi, Simone, Delogu, Giovanni (ORCID:0000-0003-0182-8267), Paolino, Marco, Brindisi, Margherita, Vallone, Alessandra, Butini, Stefania, Campiani, Giuseppe, Nannicini, Chiara, Giuliani, Germano, Anzini, Maurizio, Lamponi, Stefania, Giorgi, Gianluca, Sbardella, Diego, Ferraris, Davide M., Marini, Stefano, Coletta, Massimo, Palucci, Ivana, Minerva, Mariachiara, Delogu, Giovanni, Pepponi, Ilaria, Goletti, Delia, Cappelli, Andrea, Gemma, Sandra, Brogi, Simone, and Delogu, Giovanni (ORCID:0000-0003-0182-8267)

Abstract

The enzyme Zmp1 is a zinc-containing peptidase that plays a critical role in the pathogenicity of Mycobacterium tuberculosis. Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8-hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, N-(benzyloxy)-8-hydroxyquinoline-2-carboxamide (1 c) was found to be the most potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by kinetics studies and molecular modeling, identifying critical interactions of 1 c with the zinc ion and residues in the active site. The effect of 1 c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte-derived macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity were also assessed. Overall, inhibitor 1 c displays interesting in vitro antitubercular properties worthy of further investigation.

Published
2018

2. Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside Macrophages

Author

Stefania Butini, Delia Goletti, Ilaria Pepponi, Maurizio Anzini, Giovanni Delogu, Marco Paolino, Andrea Cappelli, Stefania Lamponi, Germano Giuliani, Davide M. Ferraris, Simone Brogi, Chiara Nannicini, Sandra Gemma, Ivana Palucci, Massimo Coletta, Mariachiara Minerva, Alessandra Vallone, Giuseppe Campiani, Diego Sbardella, Gianluca Giorgi, Stefano Marini, Margherita Brindisi, Paolino, Marco, Brindisi, Margherita, Vallone, Alessandra, Butini, Stefania, Campiani, Giuseppe, Nannicini, Chiara, Giuliani, Germano, Anzini, Maurizio, Lamponi, Stefania, Giorgi, Gianluca, Sbardella, Diego, Ferraris, Davide M, Marini, Stefano, Coletta, Massimo, Palucci, Ivana, Minerva, Mariachiara, Delogu, Giovanni, Pepponi, Ilaria, Goletti, Delia, Cappelli, Andrea, Gemma, Sandra, and Brogi, Simone

Subjects
0301 basic medicine, Models, Molecular, Mycobacterium tuberculosi, 8-hydroxyquinoline-2-hydroxamate, Mycobacterium tuberculosis, QPLD, Zmp1, metalloprotease inhibitors, Animals, Anti-Bacterial Agents, Bacterial Proteins, Humans, Hydroxamic Acids, Hydroxyquinolines, Kinetics, Macrophages, Metalloproteases, Mice, Microbial Sensitivity Tests, Molecular Structure, 01 natural sciences, Biochemistry, Virulence factor, Models, Drug Discovery, General Pharmacology, Toxicology and Pharmaceutics, Cytotoxicity, chemistry.chemical_classification, Metalloproteinase, biology, Molecular Medicine, Intracellular, Toxicology and Pharmaceutics (all), Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA, Microbiology, 03 medical and health sciences, Settore BIO/10, Pharmacology, Pharmacology, Toxicology and Pharmaceutics (all), Organic Chemistry, 010405 organic chemistry, Active site, Molecular, biology.organism_classification, 0104 chemical sciences, 030104 developmental biology, Enzyme, chemistry, biology.protein, Mycobacterium
Abstract

The enzyme Zmp1 is a zinc-containing peptidase that plays a critical role in the pathogenicity of Mycobacterium tuberculosis. Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8-hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, N-(benzyloxy)-8-hydroxyquinoline-2-carboxamide (1 c) was found to be the most potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by kinetics studies and molecular modeling, identifying critical interactions of 1 c with the zinc ion and residues in the active site. The effect of 1 c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte-derived macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity were also assessed. Overall, inhibitor 1 c displays interesting in vitro antitubercular properties worthy of further investigation.

Published
2018

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