title: Identification of novel and improved antimitotic agents derived from noscapine.
abstract: Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold more potent than noscapine in reducing cell proliferation in rapidly dividing cells.
authors.affiliation: Athersys, Inc., 3201 Carnegie Avenue, Cleveland, Ohio 44115-2634, USA. janderson@athersys.com
authors.forename: James T
authors.initials: JT
authors.lastname: Anderson
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Ting
authors.forename: Sherry
authors.initials: S
authors.lastname: Boozer
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Brunden
authors.forename: Chris
authors.initials: C
authors.lastname: Crumrine
authors.forename: Joel
authors.initials: J
authors.lastname: Danzig
authors.forename: Tom
authors.initials: T
authors.lastname: Dent
authors.forename: Laurel
authors.initials: L
authors.lastname: Faga
authors.forename: John J
authors.initials: JJ
authors.lastname: Harrington
authors.forename: William F
authors.initials: WF
authors.lastname: Hodnick
authors.forename: Steven M
authors.initials: SM
authors.lastname: Murphy
authors.forename: Gary
authors.initials: G
authors.lastname: Pawlowski
authors.forename: Robert
authors.initials: R
authors.lastname: Perry
authors.forename: Amy
authors.initials: A
authors.lastname: Raber
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Rundlett
authors.forename: Alain
authors.initials: A
authors.lastname: Stricker-Krongrad
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.forename: Youssef L
authors.initials: YL
authors.lastname: Bennani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001704:Biopolymers; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000187:drug effects; D009665:Noscapine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013237:Stereoisomerism; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001704:Biopolymers; D014404:Tubulin; D050257:Tubulin Modulators; D009665:Noscapine