Metabolism-based synthesis, biological evaluation and structure–activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors

Authors

  • Jing-Li Cheng,

    1. Ministry of Agriculture Key Laboratory of Agricultural Entomology, Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, China
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  • Xing-Rui He,

    1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China
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  • Zong-Cheng Wang,

    1. Hunan Research Institute of Chemical Industry, Changsha, China
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  • Jian-Gong Zhang,

    1. Ministry of Agriculture Key Laboratory of Agricultural Entomology, Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, China
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  • Jin-Hao Zhao,

    Corresponding author
    1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China
    • Ministry of Agriculture Key Laboratory of Agricultural Entomology, Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, China
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  • Guo-Nian Zhu

    1. Ministry of Agriculture Key Laboratory of Agricultural Entomology, Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, China
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Correspondence to: Jin-Hao Zhao, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310029, PR China. E-mail: jinhaozhao@zju.edu.cn

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 1H 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.

CONCLUSION

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. © 2012 Society of Chemical Industry

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