Inhibition of myeloperoxidase: Evaluation of 2H-indazoles and 1H-indazolones |
| |
Affiliation: | 1. Department of Life Science, National Taiwan Normal University, Taipei, Taiwan;2. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan;3. Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan;4. Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan |
| |
Abstract: | 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. |
| |
Keywords: | Myeloperoxidase Davis–Beirut reaction Structure–activity relationship Computational docking |
本文献已被 ScienceDirect 等数据库收录! |
|