Insecticidal heterolignans--tubuline polymerization inhibitors with activity against chewing pests.
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.
Frackenpohl
Jens
J
Bayer CropScience AG, Industriepark Höchst, G836, D-65926 Frankfurt am Main, Germany. Jens.Frackenpohl@bayercropscience.com
Adelt
Isabelle
I
Antonicek
Horst
H
Arnold
Christian
C
Behrmann
Patricia
P
Blaha
Nicole
N
Böhmer
Jutta
J
Gutbrod
Oliver
O
Hanke
Roman
R
Hohmann
Sabine
S
van Houtdreve
Marc
M
Lösel
Peter
P
Malsam
Olga
O
Melchers
Martin
M
Neufert
Valentina
V
Peschel
Elisabeth
E
Reckmann
Udo
U
Schenke
Thomas
T
Thiesen
Hans-Peter
HP
Velten
Robert
R
Vogelsang
Kathrin
K
Weiss
Hans-Christoph
HC
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
D007306:Insecticides; D017705:Lignans; D050257:Tubulin Modulators; D011034:Podophyllotoxin