Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency

Bioorg Med Chem Lett. 2008 Jul 1;18(13):3802-4. doi: 10.1016/j.bmcl.2008.05.032. Epub 2008 May 15.

Abstract

The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC50 values of 45, 25, and 38 nM, respectively.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical / methods*
  • DNA / chemistry*
  • Drug Design
  • Drug Screening Assays, Antitumor
  • G-Quadruplexes*
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Models, Chemical
  • Molecular Structure
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry
  • Structure-Activity Relationship
  • Thermodynamics

Substances

  • Oligonucleotides
  • DNA