Carbohydrate-based inducers of cellular stress for targeting cancer cells

Bioorg Med Chem Lett. 2016 Mar 1;26(5):1452-6. doi: 10.1016/j.bmcl.2016.01.063. Epub 2016 Jan 22.

Abstract

Small molecules that block the altered metabolism in cancer or increase the production of reactive oxygen species (ROS) are emerging as potential anti-cancer agents. Considering that various carbohydrates can be used for cellular energetics or protein N-glycosylation of which interruption can lead to cellular stress, we have synthesized and evaluated a library of N-aryl glycosides for induction of ROS and cytotoxicity in H1299 cancer cell line. Two N-aryl glycosides (K8 and H8) were identified that induce about 2-fold induction of ROS and cytotoxicity in H1299 cells. We further showed that the acetylated form of K8 (K8A) activates AMPK, and stabilizes p53 in HEK293 cells, and induce a higher cytotoxicity than 2-deoxy-d-glucose in H1299 cell line.

Keywords: 2-Deoxy-d-glucose; Cytotoxicity; N-Aryl glycoside library; Reactive oxygen species inducer.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Glycosides / chemical synthesis
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Reactive Oxygen Species / metabolism*
  • Stress, Physiological / drug effects*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Glycosides
  • Reactive Oxygen Species