Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

Abstract

Organodiselenides are an important class of compounds characterized by the presence of two adjacent covalently bonded selenium nuclei. Among them, diaryldiselenides and their parent compound diphenyl diselenide attract continuing interest in chemistry as well as in close disciplines like medicinal chemistry, pharmacology and biochemistry. A search in SCOPUS database has revealed that in the last three years 105 papers have been published on the archetypal diphenyl diselenide and its use in organic catalysis and drug tests. The reactivity of the Se-Se bond and the redox properties of selenium make diselenides efficient catalysts for numerous organic reactions, such as Bayer- Villiger oxidations of aldehydes/ketones, epoxidations of alkenes, oxidations of alcohols and nitrogen containing compounds. In addition, organodiselenides might find application as mimics of glutathione peroxidase (GPx), a family of enzymes, which, besides performing other functions, regulate the peroxide tone in the cells and control the oxidative stress level. In this review, the essential synthetic and reactivity aspects of organoselenides are collected and rationalized using the results of accurate computational studies, which have been carried out mainly in the last two decades. The results obtained in silico provide a clear explanation of the anti-oxidant activity of organodiselenides and more in general of their ability to reduce hydroperoxides. At the same time, they are useful to gain insight into some aspects of the enzymatic activity of the GPx, inspiring novel elements for rational catalyst and drug design.

Major Depressive Disorder and Oxidative Stress: In Silico Investigation of Fluoxetine Activity against ROS

“…Computational methodologies are nowadays largely employed to rationalize chemical and biochemical phenomena. Particularly, accurate mechanistic studies on the control of oxidative stress by endogenous defenses, including enzymes such as glutathione peroxidase [30][31][32], and molecular drugs that act as mimics of these enzymes [33][34][35][36][37] or as radical scavengers [38] have been reported by some of us. In this work, we investigate in silico the antioxidant activity of fluoxetine via HAT (hydrogen atom transfer) and RAF (radical adduct formation) mechanisms.…”

Nature and strength of chalcogen–π bonds

“…Recently, the chalcogen bond has received much attention due to the promising features making it amenable to application in many fields such as catalysis, ion transport and material and drug design. [22][23][24][25][26][27][28] In addition to that, a very recent survey of the PDB database showed that many protein-ligand complexes, in which the ligand contains a chalcogen atom, adopt structures that allow the formation of chalcogen bonds. 29 In this work, we focus our attention on a particular kind of bond acceptors, i.e.…”

Fluoxetine scaffold to design tandem molecular antioxidants and green catalysts

“…Besides the radical scavenging activity via HAT (Hydrogen Atom Transfer) mechanism, recently reported for uoxetine, 17 selenouoxetine and its derivatives have the capacity of reducing hydroperoxides and H 2 O 2 as GPx mimics. [23][24][25] The biological role of selenium is a long-debated issue since its identication in GPx, an enzyme able to protect cells from oxidative stress by inactivating hydroperoxides. [26][27][28][29][30] As oen happens, nature inspired medicinal chemists and synthetic selenium-based compounds were developed through the years to mimic GPx activity as well as to exert antioxidant activity through other mechanisms, such as metal binding.…”

“…[26][27][28][29][30] As oen happens, nature inspired medicinal chemists and synthetic selenium-based compounds were developed through the years to mimic GPx activity as well as to exert antioxidant activity through other mechanisms, such as metal binding. [23][24][25]31 Among GPx mimics, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is the most popular since it was employed in clinical trials. 32 Aryl and alkyl selenides, 33,34 together with aryl diselenides, [35][36][37][38] have been prepared and tested in vitro and in vivo.…”