NC-182 

NC-182 is a novel antitumor compound with a benzo[a]phenazine ring. The interaction mode of the agent with DNA and its effect on DNA conformation were systematically investigated by fluorescence, absorption and circular dichroism spectroscopy as well as viscosity titration measurements, and were compared with those of the DNA minor groove binder distamycin and the DNA base intercalator daunomycin. NC-182 was found to be a strong DNA intercalator, especially for B-form DNA, although without specificity for base pairs. The binding of NC-182 to B-DNA exhibited a biphasic behavior depending on the molar ratio of agent to DNA (r): at relatively low r values, NC-182 made the B-form structure rigid, and at higher r values, promoted the transition from B- to non-B-forms. NC-182 was also shown to promote the unwinding of Z-form DNA into B-form. Viscosity, UV 'melting' and circular dichroism experiments further showed that: (1) NC-182 intercalates to stabilize the DNA double helix structure; (2) NC-182 intercalates into the poly(dA) 2poly(dT) DNA structure to stabilize the triple helix structure, resulting in a melting point close to that of the double helix structure; the melting curves of the triple helix and double helix structures overlap at r > 0.06. These observations make an important contribution to our understanding of the biological properties of this novel benzo[a]phenazine derivative, which is a new antitumor agent suitable for both multiagent-resistant and sensitive tumors.

448.47

C₂₄H₂₄N₄O₅

106224-67-3

O=C(OC)C1=CC2=NC3=C(C(O)=C4C(C=CC=C4)=C3N=C2C=C1OC)C(NCCN(C)C)=O

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• [1]. DNA-binding characterization of a novel anti-tumour benzo[a]phenazine derivative NC-182: spectroscopic and viscometric studies