title: Antitumor agents. 111. New 4-hydroxylated and 4-halogenated anilino derivatives of 4'-demethylepipodophyllotoxin as potent inhibitors of human DNA topoisomerase II.
abstract: A series of C-4 hydroxylated and halogenated anilino derivatives of epipodophyllotoxin or 4'-demethylepipodophyllotoxin have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 11-17 and 22 are more potent than etoposide in causing DNA breakage, while compounds 11-13, 15, 16, and 20 are as active or more active than etoposide in their inhibition of the human DNA topoisomerase II. The cytotoxicity in KB cells appears to have no direct correlation with their ability to inhibit DNA topoisomerase II and to cause protein-linked DNA breaks in cells.
authors.affiliation: Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: S A
authors.initials: SA
authors.lastname: Beers
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Y H
authors.initials: YH
authors.lastname: Kuo
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: S Y
authors.initials: SY
authors.lastname: Liu
authors.forename: J Y
authors.initials: JY
authors.lastname: Chang
authors.forename: F S
authors.initials: FS
authors.lastname: Han
authors.forename: Y C
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D011034:Podophyllotoxin