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Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8\u2010hydroxyquinoline\u20102\u2010hydroxamate scaffold. Among the synthesized compounds, <jats:italic>N<\/jats:italic>\u2010(benzyloxy)\u20108\u2010hydroxyquinoline\u20102\u2010carboxamide (<jats:bold>1\u2009c<\/jats:bold>) 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 <jats:bold>1\u2009c<\/jats:bold> with the zinc ion and residues in the active site. The effect of <jats:bold>1\u2009c<\/jats:bold> on intracellular <jats:italic>Mycobacterium<\/jats:italic> survival was assayed in J774 murine macrophages infected with <jats:italic>M.\u2005tuberculosis<\/jats:italic> H37Rv or <jats:italic>M.\u2005bovis<\/jats:italic> BCG and human monocyte\u2010derived macrophages infected with <jats:italic>M.\u2005tuberculosis<\/jats:italic> H37Rv. Cytotoxicity and genotoxicity were also assessed. Overall, inhibitor <jats:bold>1\u2009c<\/jats:bold> displays interesting in\u2005vitro antitubercular properties worthy of further investigation.<\/jats:p>","DOI":"10.1002\/cmdc.201700759","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T10:24:39Z","timestamp":1516011879000},"page":"422-430","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Development of Potent Inhibitors of the <i>Mycobacterium tuberculosis<\/i> Virulence Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside Macrophages"],"prefix":"10.1002","volume":"13","author":[{"given":"Marco","family":"Paolino","sequence":"first","affiliation":[{"name":"European Research Centre for Drug Discovery and Development \u2013 NatSynDrugs \u2013 and Department of Biotechnology, Chemistry, and Pharmacy University of Siena  via Aldo Moro 1 53100 Siena 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