title: Inhibition of DNA topoisomerase II by azaelliptitoxins functionalized in the variable substituent domain.
abstract: A series of novel C11-substituted derivatives of azaelliptitoxin (azatoxin) have been synthesized and tested for their inhibitory activity against human DNA topoisomerase II. Incorporation of a C11 polyamine or amine resulted in an increase in the intercalation properties of the drug and a decrease of topoisomerase II activity. The structure-activity relationship (SAR) profile of the nonintercalating C11 anilino azatoxin class follows the SAR of the (anilino)acridine family. 11-(4-Cyanoanilino)azatoxin (14) was found to be the most active analog in this series, exhibiting approximately 10-fold higher activity than azatoxin 12 and etoposide.
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville 22901, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Tepe
authors.forename: J S
authors.initials: JS
authors.lastname: Madalengoitia
authors.forename: K M
authors.initials: KM
authors.lastname: Slunt
authors.forename: K W
authors.initials: KW
authors.lastname: Werbovetz
authors.forename: P G
authors.initials: PG
authors.lastname: Spoors
authors.forename: T L
authors.initials: TL
authors.lastname: Macdonald
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007211:Indoles; D059005:Topoisomerase II Inhibitors; C075996:azatoxin; D004247:DNA