Abstract
Four tetrademethyl isocolchicine analogs were prepared and evaluated as inhibitors of mammalian DNA topoisomerases in vitro. All compounds inhibited topoisomerase II-dependent DNA unknotting by a mechanism which did not involve “cleavable-complex” formation, N-Deacetylation as well as N-substitution with the (3′,4′,5′-trihydroxybenzoyl)-group afforded compounds which were less selective, based on their added ability to inhibit topoisomerase I-mediated DNA relaxation.
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