Fluorine in medicinal chemistry: β-fluorination of peripheral pyrrolidines attached to acridine ligands affects their interactions with G-quadruplex DNA

Org Biomol Chem. 2011 Mar 7;9(5):1328-31. doi: 10.1039/c0ob00886a. Epub 2011 Jan 10.

Abstract

Comparative X-ray structure studies reveal that C-F bond incorporation into the peripheral pyrrolidine moieties of the G-quadruplex DNA binding ligand BSU6039 leads to a distinct pyrrolidine ring conformation, relative to the non-fluorinated analogue, and with a different binding mode involving reversal of the pyrrolidinium N(+)-H orientation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemistry*
  • Crystallography, X-Ray
  • Fluorine / chemistry*
  • G-Quadruplexes*
  • Halogenation
  • Ligands
  • Pyrrolidines / chemistry*

Substances

  • 3,6-bis-(3-pyrrolidinopropionamide)acridine
  • Acridines
  • Ligands
  • Pyrrolidines
  • Fluorine