SPECTROSCOPIC INVESTIGATION ON THE INTERACTION OF NCA0424, A POTENT ANTITUMOR INDOLOQUINOXALINE DERIVATIVE, WITH DNA

NCA0424 (1), an indoloquinoxaline derivative, has a potent antitumor a ctivity against in vitro and in vivo tumor models. To elucidate its st ructure-activity relationship, the interactions with various B-form DN As were investigated by thermal denaturation, viscosity and circular d ichroism (CD) measurements. The thermal stability of the DNA duplex wa s increased by the interaction with 1, and preferable binding for alte rnative purine-pyrimidine base sequence was suggested. Comparative vis cometric measurements with ethidium bromide (an intercalator) and dist amycin (a minor groove binder) suggested that 1 is an intercalator. Th e interaction of DNA with 1 revealed a new CD band at 340-390 nm. Taki ng advantage of this induced CD band, the equilibrium binding constant s were determined for various DNAs, and the binding preference of 1 fo r the alternative purine-pyrimidine base sequence, especially for the case of guanine as purine base, was indicated. The appearance of the i nduced CD band implies the importance of 1 side chain for the effectiv e and/or stable intercalation of the aromatic ring into the DNA base p air.