Fragment-Sized EthR Inhibitors Exhibit Exceptionally Strong Ethionamide Boosting Effect in Whole-Cell Mycobacterium Tuberculosis Assays

Overview

Journal ACS Chem Biol

Publisher American Chemical Society

Specialties Biochemistry
Biology

Date 2017 Mar 18

PMID 28314097

Citations 10

Authors

Petar O Nikiforov

Michal Blaszczyk

Sachin Surade

Helena I Boshoff

Andaleeb Sajid

Vincent Delorme

Nathalie Deboosere

Priscille Brodin

Alain R Baulard

Clifton E Barry 3rd

Tom L Blundell

Chris Abell

Affiliations

Soon will be listed here.

Abstract

Small-molecule inhibitors of the mycobacterial transcriptional repressor EthR have previously been shown to act as boosters of the second-line antituberculosis drug ethionamide. Fragment-based drug discovery approaches have been used in the past to make highly potent EthR inhibitors with ethionamide boosting activity both in vitro and ex vivo. Herein, we report the development of fragment-sized EthR ligands with nanomolar minimum effective concentration values for boosting the ethionamide activity in Mycobacterium tuberculosis whole-cell assays.

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