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Updated: Jun 12, 2026

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
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Published on: April 5, 2017

Mycobacterium tuberculosis Sulfate Ester Dioxygenase Rv3406 Is Able to Inactivate the RCB18350 Compound.

Deborah Recchia1, Giovanni Stelitano1, Anna Egorova2

  • 1Department of Biology and Biotechnology "Lazzaro Spallanzani,", University of Pavia, 27100 Pavia, Italy.

ACS Infectious Diseases
|March 20, 2025
PubMed
Summary

A new compound, RCB18350, shows activity against Mycobacterium tuberculosis, including multidrug-resistant strains. Resistance to this drug involves the enzyme Rv3406, which metabolizes it into an inactive form.

Keywords:
Rv3406antitubercular drugsdrug inactivationtuberculosis

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Area of Science:

  • Microbiology
  • Medicinal Chemistry
  • Biochemistry

Background:

  • Rifampicin-resistant Mycobacterium tuberculosis poses a global health threat.
  • Developing new antitubercular drugs and understanding resistance mechanisms are critical.
  • Tuberculosis drug discovery requires novel therapeutic agents and insights into resistance.

Purpose of the Study:

  • To discover novel compounds effective against Mycobacterium tuberculosis.
  • To elucidate the mechanism of action and resistance for a newly identified compound, RCB18350.
  • To identify specific enzymes involved in RCB18350 resistance.

Main Methods:

  • Antimicrobial susceptibility testing to determine minimum inhibitory concentration (MIC).
  • Evaluation of compound activity against multidrug-resistant tuberculosis isolates.
  • Biochemical assays to investigate the metabolic fate of RCB18350 and identify resistance-mediating enzymes.

Main Results:

  • RCB18350 demonstrated potent activity against Mycobacterium tuberculosis with an MIC of 1.25 μg/mL.
  • The compound was effective against multidrug-resistant isolates.
  • Rv3406, an iron- and α-ketoglutarate-dependent dioxygenase, was identified as an enzyme that metabolizes RCB18350 into an inactive product.

Conclusions:

  • RCB18350 is a promising candidate for tuberculosis treatment, showing efficacy against resistant strains.
  • The enzyme Rv3406 plays a key role in the resistance mechanism against RCB18350.
  • Understanding this resistance mechanism can inform future drug development strategies for tuberculosis.