Structure-based virtual screening and biological evaluation of Mycobacterium tuberculosis adenosine 5'-phosphosulfate reductase inhibitors

J Med Chem. 2008 Nov 13;51(21):6627-30. doi: 10.1021/jm800571m. Epub 2008 Oct 15.


Tuberculosis is among the world's deadliest infectious diseases. APS reductase catalyzes the first committed step in bacterial sulfate reduction and is a validated drug target against latent tuberculosis infection. We performed a virtual screening to identify APSR inhibitors. These inhibitors represent the first non-phosphate-based molecules to inhibit APSR. Common chemical features lay the foundation for the development of agents that could shorten the duration of chemotherapy by targeting the latent stage of TB infection.

MeSH terms

  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Ligands
  • Models, Molecular
  • Mycobacterium tuberculosis / enzymology*
  • Oxidoreductases Acting on Sulfur Group Donors / antagonists & inhibitors*
  • Oxidoreductases Acting on Sulfur Group Donors / chemistry
  • Oxidoreductases Acting on Sulfur Group Donors / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Substrate Specificity


  • Enzyme Inhibitors
  • Ligands
  • Oxidoreductases Acting on Sulfur Group Donors
  • adenylylsulfate reductase