Voreloxin Is an Anticancer Quinolone Derivative that Intercalates DNA and Poisons Topoisomerase II
Figure 4
Voreloxin and the fused phenyl analog intercalate DNA, while the nonplanar phenyl analog does not.
A, Structures of voreloxin and the two analogs are shown, with the thiazole group of voreloxin boxed and the fused phenyl and phenyl rings highlighted by arrow or box, respectively. B and C, Agarose gels stained with ethidium bromide are shown. Intercalation was evaluated by conversion of negatively supercoiled DNA (-SC) into positively supercoiled DNA (+SC) (4B) or the conversion of relaxed plasmid DNA (Rel) to supercoiled molecules (SC) (4C). Control reactions were carried out in the absence of both drug and enzyme (labeled as DNA) or in the absence of drug but containing enzyme (labeled 0). Topoisomerase I concentration was constant. Reactions containing etoposide (100 µM) and ethidium bromide (10 µM) are included as examples of a nonintercalative and intercalative drug, respectively. Data were consistent in two independent experiments.