AIMing towards improved antitumor efficacy

Bioorg Med Chem Lett. 2015 Apr 15;25(8):1765-1770. doi: 10.1016/j.bmcl.2015.02.063. Epub 2015 Mar 3.

Abstract

Using the structure-activity relationship emerging from previous Letter, and guided by pharmacokinetic properties, new AIMs have been prepared with both improved efficacy against human glioblastoma cells and cell permeability as determined by fluorescent confocal microscopy. We present our first unambiguous evidence for telomeric G4-forming oligonucleotide anisotropy by NMR resulting from direct interaction with AIMs, which is consistent with both our G4 melting studies by CD, and our working hypothesis. Finally, we show that AIMs induce apoptosis in SNB-19 cells.

Keywords: Anthracene; DNA Quadruplex; Glioblastoma; Isoxazole; Pyrrole; Tumor paint.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Amides / metabolism
  • Amides / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Binding Sites
  • Cell Line, Tumor
  • Circular Dichroism
  • Crystallography, X-Ray
  • G-Quadruplexes
  • Humans
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • Structure-Activity Relationship
  • Telomere / chemistry

Substances

  • Amides
  • Antineoplastic Agents