Design of antitumor agents containing carbohydrate based on GLUT1, and evaluation of antiproliferative activity

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2488-2492. doi: 10.1016/j.bmcl.2017.03.094. Epub 2017 Apr 2.

Abstract

A series of novel carbohydrate-modified antitumor compounds were designed based on glucose transporter 1 (GLUT1), and evaluated for their anticancer activities against four cancer cell lines. The ribose derivatives (compound 9 and 10) exhibited modest inhibitory activity. The compound 9 significantly inhibited the migration of A549 cell and induced A549 cell apoptosis in a concentration-dependent manner. Moreover, compound 9 blocked A549 cells at the G0/G1 phase. The cellular uptake studies suggested that ribose-modified compound 9 could be taken through GLUT1 in A549 cell line.

Keywords: Anticancer; Cell uptake; Drug design; GLUT1; Saccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Binding Sites
  • Carbohydrates / chemistry*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Drug Design*
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Glucose Transporter Type 1 / chemistry
  • Glucose Transporter Type 1 / metabolism*
  • Humans
  • Molecular Docking Simulation
  • Protein Structure, Tertiary

Substances

  • Antineoplastic Agents
  • Carbohydrates
  • Glucose Transporter Type 1