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

被引：24

作者：

De Vita, Daniela ^{[1
]}

Pandolfi, Fabiana ^{[1
]}

Cirilli, Roberto ^{[2
]}

Scipione, Luigi ^{[1
]}

Di Santo, Roberto ^{[1
,3
]}

Friggeri, Laura ^{[1
]}

Mori, Mattia ^{[4
,5
]}

Fiorucci, Diego ^{[4
]}

Maccari, Giorgio ^{[4
]}

Christopher, Robert Selwyne Arul ^{[4
]}

Zamperini, Claudio ^{[4
]}

Pau, Valentina ^{[7
]}

De Logu, Alessandro ^{[7
]}

Tortorella, Silvano ^{[1
]}

Botta, Maurizio ^{[4
,6
]}

机构：

[1] Sapienza Univ Roma, Dipartimento Chim & Tecnol Farmaco, Piazzale Aldo Moro 5, I-00185 Rome, Italy

[2] Ist Super Sanita, Dipartimento Farmaco, Viale Regina Elena 299, I-00161 Rome, Italy

[3] Sapienza Univ Roma, Ist Pasteur, Fdn Cenci Bolognetti, Dipartimento Chim & Tecnol Farmaco, Piazzale Aldo Moro 5, I-00185 Rome, Italy

[4] Univ Siena, Dipartimento Biotecnol Chim & Farm, Via Aldo Moro 2, I-53019 Siena, Italy

[5] Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, Viale Regina Elena 291, I-00161 Rome, Italy

[6] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Sbarro Inst Canc Res & Mol Med, BioLife Sci Bldg,Suite 333,1900 N 12th St, Philadelphia, PA 19122 USA

[7] Univ Cagliari, Dipartimento Sci Vita & Ambiente, Via Porcell 4, I-09124 Cagliari, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 121卷

关键词：

Virtual screening; Anti-tubercular agents; Azoles; Phenyl-pyrazolopyrimidinones; BIOLOGICAL EVALUATION; ANTIMYCOBACTERIAL ACTIVITY; PYRAZOLE ANALOGS; INHIBITORS; DERIVATIVES; DESIGN; METABOLISM; CHEMISTRY; DRUGS; SAR;

D O I：

10.1016/j.ejmech.2016.05.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu g/mL respectively. These molecules represent a good starting point for further optimization of effective anti-TB agents. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：169 / 180

页数：12

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