New highly hydrosoluble and not self-aggregated perylene derivatives with three and four polar side-chains as G-quadruplex telomere targeting agents and telomerase inhibitors

Bioorg Med Chem Lett. 2007 May 1;17(9):2515-22. doi: 10.1016/j.bmcl.2007.02.021. Epub 2007 Feb 9.

Abstract

Four new perylene derivatives with three and four basic side-chains are reported here as G-quadruplex interactive compounds. The new perylene derivatives are readily soluble in water and not self-aggregated, in contrast to what happens with the previously reported two side-chain perylene derivatives. All four compounds are able to induce the G-quadruplex and to inhibit 50% of telomerase activity at about 5 microM concentration, showing a similar efficiency with respect to each other. Molecular modelling studies are presented to try to explain these findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry, Pharmaceutical / methods
  • DNA / chemistry
  • Dose-Response Relationship, Drug
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Chemical
  • Molecular Conformation
  • Nucleic Acid Conformation
  • Perylene / analogs & derivatives
  • Perylene / chemistry*
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Telomerase / antagonists & inhibitors*
  • Telomere / chemistry*

Substances

  • Enzyme Inhibitors
  • Perylene
  • DNA
  • Telomerase