title: Cytotoxic activity of triazole-containing alkyl β-D-glucopyranosides on a human T-cell leukemia cell line.
abstract: 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. Graphical AbstractTriazole-linked, glucose-based surfactants cause apoptosis, and not necrosis, at low micromolar concentrations via induction of the intrinsic apoptotic cascade.
authors.affiliation: Department of Chemistry, University of Mary Washington, 1300 College Avenue, Fredericksburg, VA 22401 USA.
authors.forename: Edward Davis
authors.initials: ED
authors.lastname: Oldham
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, Bioscience Research Building, University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 USA.
authors.forename: Larissa M
authors.initials: LM
authors.lastname: Nunes
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, Bioscience Research Building, University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Varela-Ramirez
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506 USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Rankin
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506 USA.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Knutson
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, Bioscience Research Building, University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 USA.
authors.forename: Renato J
authors.initials: RJ
authors.lastname: Aguilera
authors.affiliation: Department of Occupational and Environmental Health, The University of Iowa, UI Research Park, Iowa City, IA 52242 USA.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lehmler