Novel DNA intercalators based on the pyridazino[1 ',6 ': 1,2]pyrido[4,3-b]indol-5-inium system

A new class of DNA intercalators based on the 8H-pyridazino[1',6':1,2]pyrid o[4,3-b]indol-5-inium system in which the cationic nature of the chromophor e is provided by a brigdehead quaternary nitrogen has been obtained. These cations along with 10H-indolo[3,2-c]pyridazino[1,6-a]quinolin-5-inium, 13H- dibenz[f,h]indolo[3',2':3,4]pyrido[1,2-b]cinnolin-10-inium, and 5H-acenapht ho[1',2: 3',4']pyridazino[1',6':1,2]pyrido[4,3-b]indol-8-inium were synthes ized by the Westphal reaction of carbolinium derivatives with various 1,2-d icarbonyl compounds. When these tetra-, penta-, and heptacyclic heteroaroma tic nuclei were evaluated as DNA intercalators using UV-vis spectroscopy, v iscometric determinations, and unwinding angle determinations, we found tha t only the 8H-pyridazino[1',6':1,2]pyrido[4,3-b]indol-5-inium cations behav ed as DNA intercalators. Molecular modeling studies allowed the preferred o rientation of the intercalating chromophore within a CpG intercalation site to be explored and will provide help in the rational design of novel bis-i ntercalators based on these chromophores.