Background: 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. Results: We synthesized a series of triazole-linked (fluoro)alkyl β-glucopyranosides using the copper-catalyzed 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 β-glucopyranosides was low, with IC50 values decreasing from 1198 to 24 μM as the hydrophobic tail length increased from 8 to 16 carbons. The two alkyl β-glucopyranosides with the longest hydrophobic tails caused apoptosis by mechanisms involving mitochondrial depolarization and caspase-3 activation. Conclusions: 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.
|Journal||Chemistry Central Journal|
|State||Published - 2015|
Bibliographical noteFunding Information:
We thank Gladys Almodovar for critical review of the manuscript and cell culture expertise. We also thank the Cytometry, Screening and Imaging Core Facility at the University of Texas at El Paso (UTEP), supported by RCMI program Grant No. 2G12MD007592, to the Border Biomedical Research Center (BBRC) at UTEP, from the National Center on Minority Health and Health Disparities, a component of National Institutes of Health. The synthesis of the triazole-containing alkyl β-D-glucoyranosides 4a-g was supported by grants from the National Science Foundation (CBET-0967381/0967390) and the U.S. Department of Agriculture Biomass Research and Development Initiative (Grant Agreement 68-3A75-7-608) to HJL. The cell culture work was supported by NIGMS SCORE Grant 1SC3GM103713-01 to RJA.
© 2015 Oldham et al.; licensee Springer.
ASJC Scopus subject areas
- Chemistry (all)