DIFFERENCES IN THE TOPOISOMERASE-I CLEAVAGE COMPLEXES FORMED BY CAMPTOTHECIN AND WAKAYIN, A DNA-INTERCALATING MARINE NATURAL PRODUCT

Wakayin is a bispyrroloiminoquinone isolated from a Clavelina sp, asci dian by cytotoxicity directed fractionation, Like camptothecin, it has been found to inhibit the topoisomerase I catalyzed relaxation of sup ercoiled DNA, Wakayin enhanced cleavage complex formation at the same DNA sequences as camptothecin, Both compounds showed dose-related incr eases in cleavage complex formation, though wakayin's effect is attenu ated at high concentrations. Wakayin is a strong DNA binder, Wakayin a lso differed from camptothecin in that its cleavage complexes were muc h less stable than those of camptothecin in 0.5 M NaCl. Again in contr ast to camptothecin, wakayin stabilized cleavage complexes poorly, if at all, at 0 degrees C.