Synthesis, DNA-binding and antiproliferative properties of acridine and 5-methylacridine derivatives.
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.
Institute for Research in Biomedicine, Baldiri Reixac 10, E-08028 Barcelona, Spain. ruben.ferreira@irbbarcelona.org
Rubén
R
Ferreira
Anna
A
Aviñó
Stefania
S
Mazzini
Ramon
R
Eritja
D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D019906:Nuclear Magnetic Resonance, Biomolecular
C575323:5-methylacridine-4-carboxylic acid; D000166:Acridines; D000970:Antineoplastic Agents; D004247:DNA