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

De Vita, D;Pandolfi, F;Cirilli, R;Scipione, L;Di Santo, R;Friggeri, L;Mori, M;Fiorucci, D;Maccari, G;Christopher, RSA;Zamperini, C;Pau, V;DE LOGU, ALESSANDRO;Tortorella, S;Botta, M.

2016-01-01

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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 ligand-based 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 μg/4g/mL respectively. These molecules represent a good starting point for further optimization of effective anti-TB agents