Spectroscopic investigation on the interaction of NCA0424, a potent antitumor indoloquinoxaline derivative, with DNA.
NCA0424 (1), an indoloquinoxaline derivative, has a potent antitumor activity against in vitro and in vivo tumor models. To elucidate its structure-activity relationship, the interactions with various B-form DNAs were investigated by thermal denaturation, viscosity and circular dichroism (CD) measurements. The thermal stability of the DNA duplex was increased by the interaction with 1, and preferable binding for alternative purine-pyrimidine base sequence was suggested. Comparative viscometric measurements with ethidium bromide (an intercalator) and distamycin (a minor groove binder) suggested that 1 is an intercalator. The interaction of DNA with 1 revealed a new CD band at 340-390 nm. Taking advantage of this induced CD band, the equilibrium binding constants were determined for various DNAs, and the binding preference of 1 for the alternative purine-pyrimidine base sequence, especially for the case of guanine as purine base, was indicated. The appearance of the induced CD band implies the importance of 1 side chain for the effective and/or stable intercalation of the aromatic ring into the DNA base pair.
Ishida
T
T
Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
Mihara
Y
Y
Hama
Y
Y
Hanatani
A
A
Tarui
M
M
Doi
M
M
Nakaike
S
S
Kitamura
K
K
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D007364:Intercalating Agents / Q000494:pharmacology; D009691:Nucleic Acid Denaturation; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D014783:Viscosity
D000970:Antineoplastic Agents; D007211:Indoles; D007364:Intercalating Agents; C112900:NCA 0424; D011810:Quinoxalines; D004247:DNA