The development of new anti-tubercular agents represents a constant challenge mostly due to the insurgency of resistance to the currently available drugs. In this study, a set of 60 molecules were selected by screening the Asinex and the ZINC collections and an in house library by means of in silico ligandbased approaches. Biological assays in Mycobacterium tuberculosis H37Ra ATCC 25177 strain highlighted (±)-1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(3,4-dichlorophenyl)piperazine-1- carboxylate (5i) and 3-(4-chlorophenyl)-5-(2,4-dimethylpyrimidin-5-yl)-2-methylpyrazolo[1.5-a]pyrimidin- 7(4H)-one (42) as the most potent compounds, having a Minimum Inhibitory Concentration (MIC) of 4 and 2 ug/mL respectively. These molecules represent a good starting point for further optimization of effective anti-TB agents.

Discovery of in vitro antitubercular agents through in silico ligand-based approaches / DE VITA, Daniela; Pandolfi, Fabiana; Cirilli, Roberto; Scipione, Luigi; DI SANTO, Roberto; Friggeri, Laura; Mori, Mattia; Fiorucci, Diego; Maccari, Giorgio; Arul Christopher, Robert Selwyne; Zamperini, Claudio; Pau, Valentina; De Logu, Alessandro; Tortorella, Silvano; Botta, Maurizio. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 121:(2016), pp. 169-180. [10.1016/j.ejmech.2016.05.032]

Discovery of in vitro antitubercular agents through in silico ligand-based approaches

DE VITA, DANIELA;PANDOLFI, FABIANA;SCIPIONE, Luigi;DI SANTO, Roberto;FRIGGERI, LAURA;MORI, MATTIA;TORTORELLA, Silvano
;
2016

Abstract

The development of new anti-tubercular agents represents a constant challenge mostly due to the insurgency of resistance to the currently available drugs. In this study, a set of 60 molecules were selected by screening the Asinex and the ZINC collections and an in house library by means of in silico ligandbased approaches. Biological assays in Mycobacterium tuberculosis H37Ra ATCC 25177 strain highlighted (±)-1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(3,4-dichlorophenyl)piperazine-1- carboxylate (5i) and 3-(4-chlorophenyl)-5-(2,4-dimethylpyrimidin-5-yl)-2-methylpyrazolo[1.5-a]pyrimidin- 7(4H)-one (42) as the most potent compounds, having a Minimum Inhibitory Concentration (MIC) of 4 and 2 ug/mL respectively. These molecules represent a good starting point for further optimization of effective anti-TB agents.
Virtual screening; anti-tubercular agents; azoles; phenyl-pyrazolopyrimidinones
01 Pubblicazione su rivista::01a Articolo in rivista
Discovery of in vitro antitubercular agents through in silico ligand-based approaches / DE VITA, Daniela; Pandolfi, Fabiana; Cirilli, Roberto; Scipione, Luigi; DI SANTO, Roberto; Friggeri, Laura; Mori, Mattia; Fiorucci, Diego; Maccari, Giorgio; Arul Christopher, Robert Selwyne; Zamperini, Claudio; Pau, Valentina; De Logu, Alessandro; Tortorella, Silvano; Botta, Maurizio. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 121:(2016), pp. 169-180. [10.1016/j.ejmech.2016.05.032]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/874787
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