title: Insecticidal heterolignans--tubuline polymerization inhibitors with activity against chewing pests.
abstract: Starting from natural product podophyllotoxin 1 substituted heterolignans were identified with promising insecticidal in vivo activity. The impact of substitution in each segment of the core structure was investigated in a detailed SAR study, and variation of substituents in both aromatic moieties afforded derivatives 5 and 43 with broad insecticidal activity against lepidopteran and coleopteran species. In vitro measurements supported by modeling studies indicate that heterolignans 3-134 act as tubuline polymerization inhibitors interacting with the colchicine-binding site. Insect specific structure-activity effects were observed showing that the insecticidal SAR described herein differs from reported cytotoxicity studies.
authors.affiliation: Bayer CropScience AG, Industriepark Höchst, G836, D-65926 Frankfurt am Main, Germany. Jens.Frackenpohl@bayercropscience.com
authors.forename: Jens
authors.initials: J
authors.lastname: Frackenpohl
authors.forename: Isabelle
authors.initials: I
authors.lastname: Adelt
authors.forename: Horst
authors.initials: H
authors.lastname: Antonicek
authors.forename: Christian
authors.initials: C
authors.lastname: Arnold
authors.forename: Patricia
authors.initials: P
authors.lastname: Behrmann
authors.forename: Nicole
authors.initials: N
authors.lastname: Blaha
authors.forename: Jutta
authors.initials: J
authors.lastname: Böhmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Gutbrod
authors.forename: Roman
authors.initials: R
authors.lastname: Hanke
authors.forename: Sabine
authors.initials: S
authors.lastname: Hohmann
authors.forename: Marc
authors.initials: M
authors.lastname: van Houtdreve
authors.forename: Peter
authors.initials: P
authors.lastname: Lösel
authors.forename: Olga
authors.initials: O
authors.lastname: Malsam
authors.forename: Martin
authors.initials: M
authors.lastname: Melchers
authors.forename: Valentina
authors.initials: V
authors.lastname: Neufert
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Peschel
authors.forename: Udo
authors.initials: U
authors.lastname: Reckmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Schenke
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Thiesen
authors.forename: Robert
authors.initials: R
authors.lastname: Velten
authors.forename: Kathrin
authors.initials: K
authors.lastname: Vogelsang
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001517:Coleoptera / Q000187:drug effects; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D007915:Lepidoptera / Q000187:drug effects; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011034:Podophyllotoxin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D007306:Insecticides; D017705:Lignans; D050257:Tubulin Modulators; D011034:Podophyllotoxin