Inhibition of myeloperoxidase: Evaluation of 2H-indazoles and 1H-indazolones

Aaron Roth, Sean Ott, Kelli M. Farber, Teresa A. Palazzo, Wayne E. Conrad, Makhluf J. Haddadin, Dean J. Tantillo, Carroll E Cross, Jason P. Eiserich, Mark J. Kurth

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Myeloperoxidase (MPO) produces hypohalous acids as a key component of the innate immune response; however, release of these acids extracellularly results in inflammatory cell and tissue damage. The two-step, one-pot Davis-Beirut reaction was used to synthesize a library of 2H-indazoles and 1H-indazolones as putative inhibitors of MPO. A structure-activity relationship study was undertaken wherein compounds were evaluated utilizing taurine-chloramine and MPO-mediated H2O2 consumption assays. Docking studies as well as toxicophore and Lipinski analyses were performed. Fourteen compounds were found to be potent inhibitors with IC50 values <1 μM, suggesting these compounds could be considered as potential modulators of pro-oxidative tissue injury pertubated by the inflammatory MPO/H2O2/HOCl/HOBr system.

Original languageEnglish (US)
Pages (from-to)6422-6429
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number22
StatePublished - Nov 15 2014


  • 2H-Indazole
  • Computational docking
  • Davis-Beirut reaction
  • Myeloperoxidase
  • Structure-activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science


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