Synthesis, DNA-Binding and Antiproliferative Properties of Acridine and 5-Methylacridine Derivatives

• Main Authors: Ramon Eritja, Rubén Ferreira, Stefania Mazzini, Anna Aviñó
• Format: Article
• Language: English
• Published: MDPI AG 2012-06-01
• Series: Molecules
• Subjects: acridine; DNA-binding drugs; solid-phase synthesis; G-quadruplex; NMR
• Online Access: http://www.mdpi.com/1420-3049/17/6/7067

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.