Cytotoxic activity of triazole-containing alkyl β-D-glucopyranosides on a human T-cell leukemia cell line

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 IC(50) 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. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13065-014-0072-1) contains supplementary material, which is available to authorized users

The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea.

<p>Abstract</p> <p>Background</p> <p>G protein-coupled receptors (GPCRs) constitute one of the largest groupings of eukaryotic proteins, and represent a particularly lucrative set of pharmaceutical targets. They play an important role in eukaryotic signal transduction and physiology, mediating cellular responses to a diverse range of extracellular stimuli. The phylum Platyhelminthes is of considerable medical and biological importance, housing major pathogens as well as established model organisms. The recent availability of genomic data for the human blood fluke <it>Schistosoma mansoni </it>and the model planarian <it>Schmidtea mediterranea </it>paves the way for the first comprehensive effort to identify and analyze GPCRs in this important phylum.</p> <p>Results</p> <p>Application of a novel transmembrane-oriented approach to receptor mining led to the discovery of 117 <it>S. mansoni </it>GPCRs, representing all of the major families; 105 <it>Rhodopsin</it>, 2 <it>Glutamate</it>, 3 <it>Adhesion</it>, 2 <it>Secretin </it>and 5 <it>Frizzled</it>. Similarly, 418 <it>Rhodopsin</it>, 9 <it>Glutamate</it>, 21 <it>Adhesion</it>, 1 <it>Secretin </it>and 11 <it>Frizzled S. mediterranea </it>receptors were identified. Among these, we report the identification of novel receptor groupings, including a large and highly-diverged Platyhelminth-specific <it>Rhodopsin </it>subfamily, a planarian-specific <it>Adhesion</it>-like family, and atypical <it>Glutamate</it>-like receptors. Phylogenetic analysis was carried out following extensive gene curation. Support vector machines (SVMs) were trained and used for ligand-based classification of full-length <it>Rhodopsin </it>GPCRs, complementing phylogenetic and homology-based classification.</p> <p>Conclusions</p> <p>Genome-wide investigation of GPCRs in two platyhelminth genomes reveals an extensive and complex receptor signaling repertoire with many unique features. This work provides important sequence and functional leads for understanding basic flatworm receptor biology, and sheds light on a lucrative set of anthelmintic drug targets.</p