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

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dc.contributor.authorRoth, Aaron
dc.contributor.authorOtt, Sean P.
dc.contributor.authorFarber, Kelli M.
dc.contributor.authorPalazzo, Teresa Ann
dc.contributor.authorConrad, Wayne E.
dc.contributor.authorHaddadin, Makhluf J.
dc.contributor.authorTantillo, Dean Joseph
dc.contributor.authorCross, Carroll Edward
dc.contributor.authorEiserich, Jason P.
dc.contributor.authorKurth, Mark J.
dc.contributor.departmentDepartment of Chemistry
dc.contributor.facultyFaculty of Arts and Sciences (FAS)
dc.contributor.institutionAmerican University of Beirut
dc.date.accessioned2025-01-24T11:21:42Z
dc.date.available2025-01-24T11:21:42Z
dc.date.issued2014
dc.description.abstractMyeloperoxidase (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. © 2014 Elsevier Ltd. All rights reserved.
dc.identifier.doihttps://doi.org/10.1016/j.bmc.2014.09.044
dc.identifier.eid2-s2.0-84908381729
dc.identifier.pmid25438766
dc.identifier.urihttp://hdl.handle.net/10938/25273
dc.language.isoen
dc.publisherElsevier Ltd
dc.relation.ispartofBioorganic and Medicinal Chemistry
dc.sourceScopus
dc.subject2h-indazole
dc.subjectComputational docking
dc.subjectDavis-beirut reaction
dc.subjectMyeloperoxidase
dc.subjectStructure-activity relationship
dc.subjectBinding sites
dc.subjectCatalytic domain
dc.subjectChloramines
dc.subjectHumans
dc.subjectIndazoles
dc.subjectMolecular docking simulation
dc.subjectPeroxidase
dc.subjectProtein binding
dc.subjectTaurine
dc.subject1h indazolone derivative
dc.subject2 (4 ethynylphenyl) 3 methoxy indazole derivative
dc.subject2,3 dihydrooxazolo[3,2 b]indazole derivative
dc.subject2h indazole derivative
dc.subject3 alkoxy 2h indazole derivative
dc.subject4 aminobenzoic acid derivative
dc.subject4 aminobenzoic acid hydrazide
dc.subjectHydrobromic acid
dc.subjectHydrogen peroxide
dc.subjectHypochlorous acid
dc.subjectIndazole derivative
dc.subjectTosylchloramide sodium
dc.subjectUnclassified drug
dc.subject[1,3]oxazino[3,2 b]indazole derivative
dc.subjectChloramine derivative
dc.subjectAnalytic method
dc.subjectArticle
dc.subjectCarbon nuclear magnetic resonance
dc.subjectChlorination
dc.subjectControlled study
dc.subjectDrug determination
dc.subjectDrug structure
dc.subjectEnzyme inhibition
dc.subjectEnzyme inhibition assay
dc.subjectHydrogen peroxide scavenging assay
dc.subjectIc50
dc.subjectLipinski analysis
dc.subjectMolecular docking
dc.subjectOne pot synthesis
dc.subjectOxidative stress
dc.subjectProton nuclear magnetic resonance
dc.subjectStructure activity relation
dc.subjectTaurine chlorination assay
dc.subjectToxicity testing
dc.subjectToxicophore analysis
dc.subjectAntagonists and inhibitors
dc.subjectBinding site
dc.subjectChemistry
dc.subjectEnzyme active site
dc.subjectHuman
dc.subjectMetabolism
dc.titleInhibition of myeloperoxidase: Evaluation of 2H-indazoles and 1H-indazolones
dc.typeArticle

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