title: Antitumor agents. 100. Inhibition of human DNA topoisomerase II by cytotoxic ether and ester derivatives of podophyllotoxin and alpha-peltatin.
abstract: A principal mechanism of action of the clinical antitumor drugs etoposide (1) and teniposide (2) is the inhibition of catalytic activity of type II DNA topoisomerase and concurrent enzyme-mediated production of lethal DNA strand breaks. Substitution of the glycosidic moiety of 1 or 2 by ester and ethers, as well as the esterification and etherification of alpha-peltatin (4) including its glucosidic ethylidene and thenylidene cyclic acetals (25 and 26), has afforded compounds of much less activity than that of 1. The in vitro cytotoxicity (KB) appears to have no correlation with the inhibitory activity of the human DNA topoisomerase II.
authors.affiliation: Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: L S
authors.initials: LS
authors.lastname: Thurston
authors.forename: Y
authors.initials: Y
authors.lastname: Imakura
authors.forename: M
authors.initials: M
authors.lastname: Haruna
authors.forename: D H
authors.initials: DH
authors.lastname: Li
authors.forename: Z C
authors.initials: ZC
authors.lastname: Liu
authors.forename: S Y
authors.initials: SY
authors.lastname: Liu
authors.forename: Y C
authors.initials: YC
authors.lastname: Cheng
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004952:Esters; D004987:Ethers; D006801:Humans; D066298:In Vitro Techniques; D007624:KB Cells / Q000187:drug effects; D007945:Leukemia, Lymphoid / Q000201:enzymology; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004952:Esters; D004987:Ethers; D059005:Topoisomerase II Inhibitors; C049798:alpha-peltatin; D011034:Podophyllotoxin