Synthesis, DNA-binding and antiproliferative properties of acridine and 5-methylacridine derivatives

Molecules. 2012 Jun 8;17(6):7067-82. doi: 10.3390/molecules17067067.

Abstract

Several acridine derivatives were synthesized and their anti-proliferative activity was determined. The most active molecules were derivatives of 5-methylacridine-4-carboxylic acid. The DNA binding properties of the synthesized acridines were analyzed by competitive dialysis and compared with the anti-proliferative activities. While inactive acridine derivatives showed high selectivity for G-quadruplex structures, the most active 5-methylacridine-4-carboxamide derivatives had high affinity for DNA but showed poor specificity. An NMR titration study was performed with the most active 5-methylacridine-4-carboxamide, confirming the high affinity of this compound for both duplex and quadruplex DNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemical synthesis*
  • Acridines / chemistry
  • Acridines / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Nuclear Magnetic Resonance, Biomolecular

Substances

  • 5-methylacridine-4-carboxylic acid
  • Acridines
  • Antineoplastic Agents
  • DNA