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ID: ALA1137753

Journal: Bioorg Med Chem

Title: Insecticidal heterolignans--tubuline polymerization inhibitors with activity against chewing pests.

Authors: Frackenpohl J, Adelt I, Antonicek H, Arnold C, Behrmann P, Blaha N, Böhmer J, Gutbrod O, Hanke R, Hohmann S, van Houtdreve M, Lösel P, Malsam O, Melchers M, Neufert V, Peschel E, Reckmann U, Schenke T, Thiesen HP, Velten R, Vogelsang K, Weiss HC.

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.

CiteXplore: 19223182

DOI: 10.1016/j.bmc.2009.01.042