Ebselen (also called PZ 51, DR3305, and SPI-1005), is a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity. It acts as a mimic of

glutathione peroxidase Glutathione peroxidase (GPx) () is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid h ...

and can also react with

peroxynitrite Peroxynitrite (sometimes called peroxonitrite) is an ion with the formula ONOO−. It is a structural isomer of nitrate, Preparation Peroxynitrite can be prepared by the reaction of superoxide with nitric oxide: : It is prepared by the react ...

. It is being investigated as a possible treatment for

reperfusion injury Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ('' re-'' + '' perfusion'') after a period of ischemia or lack of oxygen (anoxia or h ...

and

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

Ménière's disease Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initial ...

hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...

and

tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...

, and

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

. Additionally, ebselen may be effective against ''Clostridioides difficile'' infections and has been shown to have antifungal activity against ''

Aspergillus fumigatus ''Aspergillus fumigatus'' is a species of fungus in the genus ''Aspergillus'', and is one of the most common ''Aspergillus'' species to cause disease in individuals with an immunodeficiency. ''Aspergillus fumigatus'', a saprotroph widespread in ...

''. Ebselen is a potent scavenger of hydrogen peroxide as well as hydroperoxides including membrane bound phospholipid and cholesterylester hydroperoxides. Several ebselen analogs have been shown to scavenge hydrogen peroxide in the presence of thiols.

Possible anti-COVID-19 activity

Preliminary studies demonstrate that Ebselen exhibits promising inhibitory activity against COVID-19 in cell-based assays. The effect was attributed to irreversible inhibition of the main protease via a covalent bond formation with the thiol group of the active center's cysteine (Cys-145).

Synthesis

Generally, synthesis of the characteristic scaffold of ebselen, the benzoisoselenazolone ring system, can be achieved either through reaction of primary amines (RNH₂) with 2-(chloroseleno)benzoyl chloride (Route I), by ''ortho''-lithiation of benzanilides followed by oxidative cyclization (Route II) mediated by cupric bromide (CuBr₂), or through the efficient Cu-catalyzed selenation / heterocyclization of o-halobenzamides, a methodology developed by Kumar ''et al.'' (Route III). Ebselen_Routes

References

{{reflist, 2 Organoselenium compounds SARS-CoV-2 main protease inhibitors