Title:Myeloperoxidase as a Target for the Treatment of Inflammatory Syndromes: Mechanisms and Structure Activity Relationships of Inhibitors
Volume: 23
Issue: 35
Author(s): Jalal Soubhye, Iyas Aldib, Cédric Delporte, Martine Prévost, François Dufrasne and Pierre Van Antwerpen
Affiliation:
Keywords:
Myeloperoxidase, reversible inhibitor, irreversible inhibitor, drug design, docking, structure-activity
relationship.
Abstract: Inflammation is an initial response of the body to a harmful stimuli
and it is achieved by the increased movement of leukocytes (especially
granulocytes) from blood into injured tissues. It is required for healing
wounds and infections. Despite their indispensable role in microbial killing,
the inflammation reactions may also cause diseases to a host such as hay
fever, atherosclerosis, and rheumatoid arthritis. The enzymes and oxidizing
species released during the inflammatory process can cause damages to the
host tissues which lead to inflammatory syndromes. The role of myeloperoxidase
(MPO) in the inflammatory reactions is well documented. It contributes
in killing the pathogens but it is also implicated in several inflammatory
syndromes such as Parkinson's disease, Alzheimer’s disease and atherosclerosis.
Thus, this enzyme has attracted more attention of the scientists and it has become a target
for drug designing. In the last decade, several reversible and irreversible MPO inhibitors
were identified as very high potent inhibitors such as fluoroalkylindole, aromatic hydroxamic
acid, thioxanthine and benzoic acid hydrazide derivatives. In this review, we tried to
illustrate the MPO inhibitors and highlight their structure activity relationship (SAR). In this
paper we also discussed the mechanism of the inhibitory effect of the most potent compounds.
