Mycobacterial tryptophan biosynthesis: A promising target for tuberculosis drug development?. Issue 23 (1st December 2019)

• Record Type: Journal Article
• Authors: Consalvi, Sara; Scarpecci, Cristina; Biava, Mariangela; Poce, Giovanna
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 23(2019)
• Publication Date: 2019-12-01
• Subjects: Tuberculosis -- Drug discovery -- Tryptophan -- M. tuberculosis -- Inhibitors; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.126731
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The biosynthetic pathways of amino acids are attractive targets for drug development against pathogens with an intracellular behavior like M. tuberculosis ( Mtb ). Indeed, while in the macrophages Mtb has restricted access to amino acids such as tryptophan (Trp). Auxotrophic Mtb strains, with mutations in the Trp biosynthetic pathway, showed reduced intracellular survival in cultured human and murine macrophages and failed to cause the disease in immunocompetent and immunocompromised mice. Herein we present recent efforts in the discovery of Trp biosynthesis inhibitors.