Pyridoxine‐Derived Organoselenium Compounds with Glutathione Peroxidase‐Like and Chain‐Breaking Antioxidant Activity

Abstract

One of the vitamin B6 vitamers, pyridoxine, was modified to incorporate selenium in various oxidation states in place of the methyl group in position 2. Such compounds were conveniently accessed by treatment of bis-4,5-(carboethoxy)-2-iodo-3-pyridinol with disodium diselenide and LiAlH4 -reduction. After work-up, selone 7 was isolated in good yield as an air-stable crystalline material. Hydrogen bonding to the neighboring hydroxyl group, as revealed by the short intramolecular Se⋅⋅⋅H distance in the crystal structure is likely to provide extra stabilization to the compound. Computational studies showed that selone 7 is more stable than the corresponding selenol tautomer by 12.2 kcal mol(-1) . Hydrogen peroxide oxidation of the selone 7 afforded diselenide 12, and, on further oxidation, seleninic acid 13. Treatment of the seleninic acid with thiophenol provided an isolable selenosulfide 14. The glutathione peroxidase-like properties of the pyridoxine-derived compounds were assessed by using the coupled reductase method. Seleninic acid 13 was found to be twofold more active than ebselen. The chain-breaking capacity of the pyridoxine compounds were studied in a water/chlorobenzene membrane model containing linoleic acid as an oxidizable substrate and N-acetylcysteine as a thiol reducing agent. Diselenide 15 could match α-tocopherol when it comes to reactivity towards peroxyl radicals and inhibition time.

Effect of a Bromo Substituent on the Glutathione Peroxidase Activity of a Pyridoxine-like Diselenide

“…In the case of pyridoxine-derived diselenide 3b, such a selone was in fact isolable and the structure determined by X-ray crystallography. 11 Diselenides 3b and 4c were both two-fold more active than ebselen when evaluated in the coupled reductase assay. With the perspective to get some more insight into the structural requirements for the high GPxactivity of pyridoxine-derived diselenides and improve the performance of compound 3, we have introduced bromine into the remaining vacant pyridinolic position 6.…”

Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity

“…Organotellurium compounds have been used as immunomodulatory, anti-inflammatory, and anti-apoptotic in Parkinson’s and diabetes models [28,29]. Previously, we synthesized organic compounds containing Se or Te which showed excellent antioxidative behavior [30,31,32,33,34]. These regenerable compounds greatly inhibited the rate of linoleic acid peroxidation in a two-phase peroxidation system, and showed GPx-like behavior in model systems.…”

Contrasting Reactivity of 2‐chloro‐1‐formyl‐3‐hydroxymethylenecyclohexene and its Schiff Bases towards Disodium Diselenide: Isolation of Selenospirocycles versus Azapentalenes

“…In this context, the procedure reported by Thomson et al . has been widely used in various organochalcogen transformation reactions– as a source of Na 2 Se 2 . When freshly prepared 5‐alkyl‐2‐chloro‐1‐formyl‐3‐hydroxymethylenecyclohexenes {alkyl= H ( 22 ), Me ( 23 )}, were treated with in situ generated Na 2 Se 2 in presence of hexamethylphosphoramide (HMPA) in THF under reflux condition and the reaction time was extended from 7 h to 18 h, in addition to the expected 1,6‐dioxa‐6a‐selenapentalene, 11 and 1‐oxa‐6,6aλ 4 ‐diselenapentalene, 12 , a third product appeared as the prominent fraction (as monitored by thin layer chromatography).…”