Terbenzimidazoles are a class of anticancer agents that bind to the minor groove of DNA, and block topoisomerase I (TOP1) from unknotting DNA duplexes during DNA replication. In so doing, they stimulate TOP1-mediated DNA fragmentation, which ultimately leads to tumor cell death. To effectively induce tumor cell death, anticancer agents must bind the duplex DNA of the tumor cell at a threshold concentration. This threshold concentration is impacted by the affinity of the agents for the DNA targets as well as the propensity of the agents to self-associate. The DNA affinity properties of three terbenzimidazole analogs (YX-I-34, WF-V-53, and WF-IV-11) were determined by concentration-dependent spectrofluorimetry. In addition, the self-association properties of the same three terbenzimidazole analogs were determined by concentration-dependent spectrophotometry. Preliminary results reveal the following hierarchy of DNA affinity:

YX-I-34 > WF-V-53 > WF-IV-11

Moreover, YX-I-34 and WF-V-53 exhibit an increased propensity for self-association relative to WF-IV-11.