title: Antitumor agents--CLI. Bis(helenalinyl)glutarate and bis(isoalantodiol-B)glutarate, potent inhibitors of human DNA topoisomerase II.
abstract: Evaluation of a number of cytotoxic antitumor sesquiterpene lactones and their derivatives has led to the discovery of bis(helenalinyl)glutarate (4) and bis(isoalantodiol-B)glutarate (10) as potent inhibitors of human-derived topoisomerase II. Unlike etoposide, which inhibits by preventing the DNA rejoining process, compounds 4 and 10 inhibit topoisomerase II without causing DNA breakage. The structure-activity relationships of 4, 10, and related compounds are discussed.
authors.affiliation: Natural Products Laboratory, Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: L M
authors.initials: LM
authors.lastname: Yang
authors.forename: T T
authors.initials: TT
authors.lastname: Lee
authors.forename: Y C
authors.initials: YC
authors.lastname: Shen
authors.forename: D C
authors.initials: DC
authors.lastname: Zhang
authors.forename: D J
authors.initials: DJ
authors.lastname: Pan
authors.forename: A T
authors.initials: AT
authors.lastname: McPhail
authors.forename: D R
authors.initials: DR
authors.lastname: McPhail
authors.forename: S Y
authors.initials: SY
authors.lastname: Liu
authors.forename: D H
authors.initials: DH
authors.lastname: Li
mesh_terms: D002460:Cell Line; D004247:DNA / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; D059005:Topoisomerase II Inhibitors; C089679:bis(helenalinyl)glutarate; C089680:bis(isoalantodiol-B)glutarate; C089681:isoallantolactone epoxide; D004247:DNA