Sulfenic acids as reactive intermediates in xenobiotic metabolism

Abstract

Sulfenic acid reactive intermediates are formed during the oxidation of cysteine residues of proteins and play key roles in enzyme catalysis, redox homeostasis and regulation of cell signalling. However few data are presently available on the formation and fate of sulfenic acids as reactive intermediates during the metabolism of xenobiotics. This article is a review of the xenobiotic metabolism situations in which the intermediate formation of a sulfenic acid has been reported. Formation of these intermediates has been either proposed on the basis of the isolation of products possibly deriving from sulfenic acids or shown after trapping of the sulfenic acid by specific nucleophiles. This review indicates the different mechanisms by which a sulphur-containing xenobiotic can be metabolized with the intermediate formation of a sulfenic acid. It also indicates the different possible fates of these sulfenic acids that have been reported in the literature. Finally, it discusses the possible implications of the formation of xenobiotic-derived sulfenic acid reactive metabolites in pharmacology and toxicology.

Computational Approach to Structural Alerts: Furans, Phenols, Nitroaromatics, and Thiophenes

“…21,64–66 Formation of reactive, electrophilic intermediates by the oxidative metabolism of thiophenes can induce toxicity, as reported for suprofen and tienilic acid. 65–70 On the other hand, thiophene-containing drugs like eprosartan and rivaroxaban are neither bioactivated nor toxic.…”

“…These pathways yield electrophilic, unstable thiophene S-oxides, 64 thiophene epoxides, 69 and sulfenic acids. 66 Notably, mass spectrometry experiments cannot reliably determine which bioactivation pathway leads to reactive metabolites because the thiophene S-oxide and the thiophene epoxide have the same mass and charge. This creates some ambiguity in the literature about the exact pathway by which some thiophenes are bioactivated.…”

Ameliorative Effects of Taurine Against Methimazole-Induced Cytotoxicity in Isolated Rat Hepatocytes

“…This could indicate that other methimazole metabolites other than N -methylthiourea are responsible for ROS formation induced by this drug. In previous investigations, it has been shown that the N -methylthiourea produced during methimazole metabolism is further metabolized to reactive metabolites, which are capable of causing cytotoxicity [16, 17]. The protective effect of taurine against N -methylthiourea cytotoxicity in rat hepatocytes could be capable of inactivating these reactive metabolites.…”

The Postulated Hepatotoxic Metabolite of Methimazole Causes Mitochondrial Dysfunction and Energy Metabolism Disturbances in Liver

“…40 Sulfonic and sulfenic acids are reactive electrophilic species which are capable of interacting with several intracellular targets such as different proteins. 41,42 In the current study, we found that NMT administration significantly damaged liver mitochondria both in vitro and in vivo. NMT reactive metabolites might also be involved in the mitochondrial injury induced by this chemical in vivo (Figure 7).…”