Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.11.1.7 (
peroxidase
)
65,474
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and promote local inflammation, which contributes to the progression of the atheromatous plaque. The key role of
myeloperoxidase
(
MPO
) in this process is related to its ability to modify
APO B-100
in the intima and at the surface of endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was designed and synthesized by exploiting the structure-based docking of 5-fluorotryptamine, a known
MPO
inhibitor. In vitro assays were used to study the effects of these compounds on the inhibition of
MPO
-mediated taurine chlorination and oxidation of LDLs. The kinetics of the interaction between the
MPO
redox intermediates, Compounds I and II, and these inhibitors was also investigated. The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no substituent on the amino group. The mode of binding of these analogues and the mechanism of inhibition is discussed with respect to the structure of
MPO
and its halogenation and
peroxidase
cycles.
...
PMID:Structure-based design, synthesis, and pharmacological evaluation of 3-(aminoalkyl)-5-fluoroindoles as myeloperoxidase inhibitors. 2109 Jun 82
