title: Antitumor agents. Part 230: C4'-esters of GL-331 as cytotoxic agents and DNA topoisomerase II inhibitors.
abstract: Three C4'-acyl derivatives (5-7) of GL-331 (4) were synthesized and evaluated for cytotoxic and DNA topoisomerase II (topo II) inhibitory activity. All three compounds were cytotoxic against KB and KB-7d cells. Compounds 5 and 7, but not 6, were potent inhibitors of the DNA topoisomerase II in vitro and this relative activity ranking was maintained for cytotoxicity, in vitro cell growth inhibition, and ability to induce cellular double-strand DNA breaks. These results provided new information on the structure-activity relationships of the C4' molecular area of 4-analogues.
authors.affiliation: Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Han
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Xiao
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005047:Etoposide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; C121391:GL 331; D005047:Etoposide