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Bioorg Med Chem Lett. 2019 Dec 1;29(23):126731. doi: 10.1016/j.bmcl.2019.126731. Epub 2019 Oct 4.

Mycobacterial tryptophan biosynthesis: A promising target for tuberculosis drug development?

Author information

1
Department of Chemistry and Technologies of Drug, Sapienza University of Rome, piazzale A. Moro 5, 00185 Rome, Italy.
2
Department of Chemistry and Technologies of Drug, Sapienza University of Rome, piazzale A. Moro 5, 00185 Rome, Italy. Electronic address: giovanna.poce@uniroma1.it.

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.

KEYWORDS:

Drug discovery; Inhibitors; M. tuberculosis; Tryptophan; Tuberculosis

PMID:
31627992
DOI:
10.1016/j.bmcl.2019.126731

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