title: Synthesis and biological activities of topopyrones.
abstract: Structure-activity studies were employed to investigate the stabilization of DNA-topoisomerases I and II covalent binary complexes by topopyrone analogues. The synthesis of five new topopyrone derivatives and study of their ability to stabilize DNA-topoisomerase I and DNA-topoisomerase II covalent binary complexes are described. The biochemical assays suggest that the orientation of the fused 1,4-pyrone ring and halogen substituents contribute importantly to the overall potency of the topopyrones as topoisomerase poisons.
authors.affiliation: Center for BioEnergetics, Biodesign Institute, Arizona State University, Tempe, Arizona 85287-6301, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Zaleski
authors.forename: Rumit
authors.initials: R
authors.lastname: Maini
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Leiris
authors.forename: Mark A
authors.initials: MA
authors.lastname: Elban
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D000880:Anthraquinones / Q000737:chemistry; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000880:Anthraquinones; D011753:Pyrones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II