Dataset Information

Oxadiazolone derivatives against M. tuberculosis

ABSTRACT: Oxadiazolone (OX) derivatives have been investigated for their antimycobacterial activity against three pathogenic slow-growing mycobacteria: Mycobacterium marinum, Mycobacterium bovis BCG and the avirulent Mycobacterium tuberculosis (M. tb) mc26230. The encouraging MIC values obtained prompted us to test them against virulent M. tb H37Rv growth either in broth medium or inside macrophages. The OX compounds displayed a diversity of action and were found to act either on extracellular M. tb growth only with moderated MIC, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth. One OX derivatives, HPOX, was selected and used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 18 potential candidates, all being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA, TesA, KasA and MetA have been reported as essential for in vitro growth of M. tb and/or its survival and persistence inside macrophages. Overall, our findings support the assumption that OX derivatives may represent a novel class of multi-target inhibitors leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser- and Cys-containing enzymes involved in various important physiological processes.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mycobacterium Tuberculosis H37rv

SUBMITTER: Luc Camoin

LAB HEAD: Luc Camoin

PROVIDER: PXD010255 | Pride | 2018-09-25

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Desthio_Beads_Rep1.raw	Raw
	Desthio_Beads_Rep1_180104201141.raw	Raw
	Desthio_Beads_Rep1_180104224733.raw	Raw
	Desthio_Beads_Rep2.raw	Raw
	Desthio_Beads_Rep2_180107094624.raw	Raw

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Publications

Oxadiazolone derivatives, new promising multi-target inhibitors against M. tuberculosis.

Nguyen Phuong Chi PC Delorme Vincent V Bénarouche Anaïs A Guy Alexandre A Landry Valérie V Audebert Stéphane S Pophillat Matthieu M Camoin Luc L Crauste Céline C Galano Jean-Marie JM Durand Thierry T Brodin Priscille P Canaan Stéphane S Cavalier Jean-François JF

Bioorganic chemistry 20180829

A set of 19 oxadiazolone (OX) derivatives have been investigated for their antimycobacterial activity against two pathogenic slow-growing mycobacteria, Mycobacterium marinum and Mycobacterium bovis BCG, and the avirulent Mycobacterium tuberculosis (M. tb) mc<sup>2</sup>6230. The encouraging minimal inhibitory concentrations (MIC) values obtained prompted us to test them against virulent M. tb H37Rv growth either in broth medium or inside macrophages. The OX compounds displayed a diversity of act ...[more]

PMID: 30212765

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