Structure-associated Functional Control of TX-1877 Series by Glyco-conjugation

Anticancer Res. 2018 Jul;38(7):4241-4245. doi: 10.21873/anticanres.12720.

Abstract

Background/aim: Sugar molecules are often used as a tool to structurally modify chemical compounds. The features of synthesized sugar-conjugated TX-1877 derivatives were herein examined.

Materials and methods: The molecular stabilities (reactivity) and hydrophobicities of sugar (e.g., monosaccharide and tetra-O-acetylated monosaccharide)-conjugated TXs were analyzed using a molecular simulation (e.g. molecular mechanics (MM) and molecular orbital (MO) analysis).

Results: The hydrophobicities of TX-1877 derivatives were increased by tetra-O-acetylation, and TX-2244 exhibited the most potent radiosensitizing activity (enhancement ratio: ER=2.30).

Conclusion: The conformations and hydrophobicities of chemical compounds may be controlled by adding monosaccharide- and tetra-O-acetyl-conjugated sugars to TX-1877.

Keywords: Molecular design; TX-1877; structure glyco-conjugation.

MeSH terms

  • Animals
  • Cell Line
  • Drug Design*
  • Glycosylation
  • Mice
  • Nitroimidazoles / chemistry*
  • Radiation-Sensitizing Agents / chemistry*
  • Structure-Activity Relationship*

Substances

  • 2-nitroimidazole acetamide
  • Nitroimidazoles
  • Radiation-Sensitizing Agents