Ebselen and Analogues: Pharmacological Properties and Synthetic Strategies for Their Preparation

Abstract

Ebselen is the leader of selenorganic compounds, and starting from its identification as mimetic of the key antioxidant enzyme glutathione peroxidase, several papers have appeared in literature claiming its biological activities. It was the subject of several clinical trials and it is currently in clinical evaluation for the treatment of COVID-19 patients. Given our interest in the synthesis and pharmacological evaluation of selenorganic derivatives with this review, we aimed to collect all the papers focused on the biological evaluation of ebselen and its close analogues, covering the timeline between 2016 and most of 2021. Our analysis evidences that, even if it lacks specificity when tested in vitro, being able to bind to every reactive cysteine, it proved to be always well tolerated in vivo, exerting no sign of toxicity whatever the administered doses. Besides, looking at the literature, we realized that no review article dealing with the synthetic approaches for the construction of the benzo[d][1,2]-selenazol-3(2H)-one scaffold is available; thus, a section of the present review article is completely devoted to this specific topic.

“Green Is the Color”: An Update on Ecofriendly Aspects of Organoselenium Chemistry

“…The use of organoselenium compounds as bioinspired catalyst for chemical transformations can be traced back to 1984, when Sies demonstrated that ebselen was able to mimic the activity of the key antioxidant enzyme glutathione peroxidase (GPx). This selenoenzyme removes harmful peroxides (H 2 O 2 or organic peroxides) from the cell using them to convert glutathione (GSH) into the corresponding disulfide and leading to the formation of harmless molecules, such as water or alcohols [ 129 , 130 , 131 ]. After this milestone, several research groups focused their attention on the preparation of small molecules acting as GPx-mimics to be exploited for pharmacological or synthetic organic chemistry purposes [ 4 , 132 , 133 ].…”

Attachment of Chiral Functional Groups to Modify the Activity of New GPx Mimetics

“…To date, a multitude of GPx mimetics possessing an organoselenium moiety that imitates the characteristic activity of L -Sec was presented and proved efficient in both in vitro and in vivo assays [ 11 , 12 ]. Among them, N -substituted benzisoselenazolones, represented by the versatile potential selenotherapeutic Ebselen, create the most explored group of derivatives with several chiral examples, including functionalized amino acids 4 and 5 [ 13 , 14 ], sugars 6 [ 15 ], alkaloids 7 [ 16 ], alcohols 8 [ 17 ] and terpenes 9 and 10 [ 18 ] ( Scheme 1 ).…”

A Review of Different Vaccines and Strategies to Combat COVID-19

“…Ebselen (2-phenyl-1,2-benzoisoselenazol-3(2H)-one), an organoselenium compound with hydroperoxide- and peroxynitrite-reducing activity, acts by inhibiting the main viral protease, Mpro. It has proven potential beneficial effects against COVID-19 [ 146 , 147 , 148 , 149 , 150 ].…”