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.| File | Dimensione | Formato | |
|---|---|---|---|
|
DeVita_Discovery_2016.pdf
solo gestori archivio
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
960.65 kB
Formato
Adobe PDF
|
960.65 kB | Adobe PDF | Contatta l'autore |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
