Synthesis and toxicity profile in 293 human embryonic kidney cells of the β D-glucuronide derivatives of ortho-, meta- and para-cresol.

Synthesis and toxicity profile in 293 human embryonic kidney cells of the β D-glucuronide derivatives of ortho-, meta- and para-cresol. Carbohydr Res. 2020 Dec 17;:108225 Authors: London JA, Wang ECS, Barsukov IL, Yates EA, Stachulski AV Abstract The formation of β-glucuronides is a major route by which mammals detoxify and remove breakdown products, such as l-tyrosine, as well as many xenobiotics, from their systems. In humans, dietary l-tyrosine is broken down largely by the action of the anaerobic gut bacterium C. difficile to p-cresol, providing a competitive advantage in the gut microbiota. Ortho- (o-) and meta- (m-), cresols, also present in the environment, may share a common degradative pathway. Relatively little work has been done on cresyl glucuronides. Here, a direct synthesis of o-, m-, and p-cresyl β-D-glucuronides from methyl 1,2,3,4 tetra-O-acetyl-β-d-glucuronate and the respective cresol employing trimethylsilyltriflate as promoter is presented. The protected intermediates were hydrolysed using aqueous sodium carbonate to yield the cresyl β-glucuronides. The toxicities of the o-, m- and p-cresyl β-D-glucuronides were compared. All three were less toxic to HEK293 cells than their respective cresol precursors: toxicity followed the order o < m < p for Na+ salts and o < p < m for Ca2+ salts. The m-cresyl-glucuronide Ca2+ salt and p-cresyl-glucuronide Na+ salt reduced colony formation by 11% and...
Source: Carbohydrate Research - Category: Genetics & Stem Cells Authors: Tags: Carbohydr Res Source Type: research