title: Synthesis and biological evaluation of tetrademethyl isocolchicine derivatives as inhibitors of DNA topoisomerase action in vitro.
abstract: Four tetrademethyl isocolchicine analogs were prepared and evaluated as inhibitors of mammalian DNA topoisomerase 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.
authors.affiliation: Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
authors.forename: K F
authors.initials: KF
authors.lastname: Bastow
authors.forename: H
authors.initials: H
authors.lastname: Tatematsu
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Fukushima
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D003078:Colchicine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C059352:isocolchicine; D004247:DNA; D003078:Colchicine