Differences in the topoisomerase I cleavage complexes formed by camptothecin and wakayin, a DNA-intercalating marine natural product

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Abstract
Wakayin is bispyrroloiminoquinone isolated from a Clavelina sp. ascidian by cytotoxicity directed fractionation. Like camptothecin, it has been found to inhibit the topoisomerase I catalyzed relaxation of supercoiled DNA. Wakayin enhanced cleavage complex formation at the same DNA sequences as camptothecin. Both compounds showed dose-related increases in cleavage complex formation, though wakayin's effect is attenuated at high concentrations. Wakayin is a string DNA binder. Wakayin also differed from camptothecin in that its cleavage complexes were much less stable than those of camptothecin in 0.5 M NaCl. Again in contrast to camptothecin, wakayin stabilized cleavage complexes poorly, if at all, at 0 degree C.

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