A new ionizable chromophore of 1,4-bis(alkylamino)benzo[g]phthalazine which interacts with DNA by intercalation.
The tricyclic heteroaromatic nucleus of 1,4-bis(alkylamino)benzo[g]phthalazine can be protonated at physiological pH, depending on the nature of the side chains. The interaction of the 3-methoxypropyl derivative with calf thymus and closed, circular DNA has been studied with UV-vis spectroscopy and NMR. The effect of drug binding on the topology of closed, circular DNA was determined by topoisomerase-I catalyzed relaxation of the complex followed by gel electrophoresis. The results strongly support intercalative binding and suggest that this series of compounds are promising targets for anticancer activity evaluation.
Pons
M
M
Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, Spain.
Campayo
L
L
Martínez-Balbas
M A
MA
Azorin
F
F
Navarro
P
P
Giralt
E
E
D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D007364:Intercalating Agents / Q000138:chemical synthesis*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011061:Poly A / Q000378:metabolism; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D007364:Intercalating Agents; D010793:Phthalazines; C067055:1,4-bis(methoxypropylamino)benzophthalazine; D011061:Poly A; D004247:DNA