Coelenterazine (marine bioluminescent substrate): a source of inspiration for the discovery of novel antioxidants.
Coelenterazine and derivatives were initially considered in the scientific community for their (bio)luminescent properties. Now, another interest of such hetero-bicycles has been pointed out by the discovery of remarkable antioxidative properties, and an unique mode of action as a "cascade": the mother-compound (imidazolopyrazinone) is transformed by ROS into a daughter-compound (2-amino-pyrazine) also endowed with antioxidative properties. This review illustrates the therapeutic potential of synthetic imidazolopyrazinones (coelenterazine analogues): chemical reactivity assays with singulet oxygen, radical anion superoxide, peroxynitrite, and radicals formed during lipid and LDL peroxidation, cellular tests of protection against oxidative stress using keratinocyte, hepatocyte, neuronal and erythrocyte cells, and finally in vivo evaluation in a hamster model of ischemia-reperfusion, are fully described.
Dubuisson
M L N
ML
Unité de Biologie Animale, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Rees
J-F
JF
Marchand-Brynaert
J
J
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D015195:Drug Design; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000737:chemistry; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D011837:Radiation-Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry
D000975:Antioxidants; D007093:Imidazoles; D018696:Neuroprotective Agents; D011719:Pyrazines; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D013481:Superoxides; D030421:Peroxynitrous Acid; C017144:coelenterazine