Simple glycoside surfactants represent a class of chemicals that are produced from renewable raw materials. They are considered to be environmentally safe and, therefore, are increasingly used as pharmaceuticals, detergents, and personal care products. Although they display low to moderate toxicity in cells in culture, the underlying mechanisms of surfactant-mediated cytotoxicity are poorly investigated. In this study, the authors synthesised a series of triazole-linked (fluoro)alkyl ?-glucopyranosides using the copper-catalysed azide-alkyne reaction, one of many popular “click” reactions that enable efficient preparation of structurally diverse compounds, and investigate the toxicity of this novel class of surfactant in the Jurkat cell line. Similar to other carbohydrate surfactants, the cytotoxicity of the triazole-linked alkyl ?-glucopyranosides was low, with IC50 values decreasing from 1198 to 24 ?M as the hydrophobic tail length increased from 8 to 16 carbons. The two alkyl ?-glucopyranosides with the longest hydrophobic tails caused apoptosis by mechanisms involving mitochondrial depolarisation and caspase-3 activation. The authors concluded that triazole-linked, glucose-based surfactants 4a-g and other carbohydrate surfactants may cause apoptosis, and not necrosis, at low micromolar concentrations via induction of the intrinsic apoptotic cascade; however, additional studies are needed to fully explore the molecular mechanisms of their toxicity.
Authors: Oldham ED, Nunes LM(2), Varela-Ramirez A, Rankin SE, Knutson BL, Aguilera RJ, Lehmler HJ. ;Full Source: Chemistry Central Journal. 2015 Feb 1;9:3. doi: 10.1186/s13065-014-0072-1. eCollection 2015. ;