title: Metabolism-based synthesis, biological evaluation and structure-activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors.
abstract: BACKGROUND
  In previous studies, scientists found that, when spirotetramat was introduced into plants or animals, it was mainly metabolised at positions C-4 and C-8. That is to say, these two functional positions potentially played an important role in spirotetramat's bioactivities. In order to develop novel insecticides or miticides, the present authors designed and synthesised 35 spirotetramat analogues based on metabolite structures.
  
  
  RESULTS
  All of the analogues have been identified on the basis of (1)H NMR, ESI-MS and elemental analysis data. The activities of these analogues were evaluated against three organisms, and biological assays indicated that compounds 5f, 5h and 5u possessed better insecticidal activities against bean aphids (Aphis fabae) than the lead compound spirotetramat. The LC50 of 5f, 5h and 5u against bean aphids reached 0.42, 0.28 and 2.53 mg L(-1) respectively. Moreover, some compounds possessed comparable activities against carmine spider mite (Tetranychus cinnabarinus) and oriental armyworm (Mythimna sepatara) with spirotetramat. The structure-activity relationships (SARs) indicated that the flexible bridge at position C-4 of spirotetramat was important for its bioactivities, and the size of the group at position C-8 would have great influence on the activities. Furthermore, the log P values lower than 6.0 may be favourable for insecticidal activities.
  
  
  CONCLUSIONS
  The present work demonstrates that some spirotetramat analogues can be used as potential lead compounds for developing novel insecticides, and preliminary SAR analysis would provide information for the utilisation of spirotetramat analogues as potential lipid biosynthesis inhibitors.
authors: Ministry of Agriculture Key Laboratory of Agricultural Entomology, Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, China.
authors: Jing-Li
authors: JL
authors: Cheng
authors: Xing-Rui
authors: XR
authors: He
authors: Zong-Cheng
authors: ZC
authors: Wang
authors: Jian-Gong
authors: JG
authors: Zhang
authors: Jin-Hao
authors: JH
authors: Zhao
authors: Guo-Nian
authors: GN
authors: Zhu
mesh_terms: D000818:Animals; D001042:Aphids / Q000187:drug effects / Q000378:metabolism; D001372:Aza Compounds / Q000737:chemistry* / Q000633:toxicity*; D001681:Biological Assay; D015195:Drug Design; D007306:Insecticides / Q000737:chemistry* / Q000633:toxicity*; D008055:Lipids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015394:Molecular Structure; D009036:Moths / Q000187:drug effects / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D040102:Tetranychidae / Q000187:drug effects / Q000378:metabolism
chemical_list: D001372:Aza Compounds; D007306:Insecticides; D008055:Lipids; D013141:Spiro Compounds; C570705:spirotetramat
keywords: insecticidal activity; metabolism; spirotetramat analogues; structure-activity relationships