2. Academic Validation
  3. Aglycone Ebselen and β-d-Xyloside Primed Glycosaminoglycans Co-contribute to Ebselen β-d-Xyloside-Induced Cytotoxicity

Aglycone Ebselen and β-d-Xyloside Primed Glycosaminoglycans Co-contribute to Ebselen β-d-Xyloside-Induced Cytotoxicity

  • J Med Chem. 2018 Apr 12;61(7):2937-2948. doi: 10.1021/acs.jmedchem.7b01835.
Yang Tang 1 2,  Siqi Zhang 1,  Yajing Chang 1 2,  Dacheng Fan 1,  Ariane De Agostini 3,  Lijuan Zhang 2,  Tao Jiang 1 4
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy , Ocean University of China , Qingdao 266071 , P. R. China.
  • 2 Medical Systems Biology Center for Complex Diseases , Affiliated Hospital of Qingdao University , Qingdao 266003 , P. R. China.
  • 3 Department of Gynecology and Obstetrics , Geneva University Hospitals and University of Geneva , Geneva 14 , Switzerland.
  • 4 Laboratory for Marine Drugs and Bioproducts of Qingdao National of Laboratory for Marine Science and Technology , Qingdao 266003 , P. R. China.
PMID: 29584939 DOI: 10.1021/acs.jmedchem.7b01835
Abstract

Most β-d-xylosides with hydrophobic aglycones are nontoxic primers for glycosaminoglycan assembly in animal cells. However, when Ebselen was conjugated to d-xylose, d-glucose, d-galactose, and d-lactose (8A-D), only Ebselen β-d-xyloside (8A) showed significant cytotoxicity in human Cancer cells. The following facts indicated that the aglycone Ebselen and β-d-xyloside primed glycosaminoglycans co-contributed to the observed cytotoxicity: 1. Ebselen induced S phase cell cycle arrest, whereas 8A induced G2/M cell cycle arrest; 2. 8A augmented early and late phase Cancer cell Apoptosis significantly compared to that of Ebselen and 8B-D; 3. Both 8A and phenyl-β-d-xyloside primed glycosaminoglycans with similar disaccharide compositions in CHO-pgsA745 cells; 4. Glycosaminoglycans could be detected inside of cells only when treated with 8A, indicating Ebselen contributed to the unique property of intracellular localization of the primed glycosaminoglycans. Thus, 8A represents a lead compound for the development of novel antitumor strategy by targeting glycosaminoglycans.

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