Myeloperoxidase as a Target for the Treatment of Inflammatory Syndromes: Mechanisms and Structure Activity Relationships of Inhibitors.
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.
Laboratoire de Chimie Pharmaceutique Organique, Faculté de Pharmacie, Université Libre de Bruxelles, Campus plaine, CP 205/5, 1050 Brussels, Belgium. jsoubhye@ulb.ac.be.
Jalal
J
Soubhye
Iyas
I
Aldib
Cédric
C
Delporte
Martine
M
Prévost
François
F
Dufrasne
Pierre Van
PV
Antwerpen
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy / Q000473:pathology; D047188:Chalcones / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D062105:Molecular Docking Simulation; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
D047188:Chalcones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009195:Peroxidase