Virtual screening identifies a novel piperazine-based insect juvenile hormone agonist

• Yokoi Taiyo

  Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University

• Nabe Taku

  Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University

• Horoiwa Shinri

  Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University

• Hayashi Ken’ichiro

  Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University

• Ito-Harashima Sayoko

  Department of Biology, Graduate School of Science, Osaka Prefecture University

• Yagi Takashi

  Department of Biology, Graduate School of Science, Osaka Prefecture University

• Nakagawa Yoshiaki

  Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University

• Miyagawa Hisashi

  Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University

抄録

Juvenile hormone (JH) agonists constitute a subclass of insect growth regulators and play important roles in insect pest management. In this work, a multi-step virtual screening program was executed to find novel JH agonists. A database of 5 million purchasable compounds was sequentially processed with three computational filters: (i) shape and chemical similarity as compared to known JH-active compounds; (ii) molecular docking simulations against a Drosophila JH receptor, methoprene-tolerant; and (iii) free energy calculation of ligand–receptor binding using a modified MM/PBSA (molecular mechanics/Poisson–Boltzmann surface area) protocol. The 11 candidates that passed the three filters were evaluated in a luciferase reporter assay, leading to the identification of a hit compound that contains a piperazine ring system (EC₅₀=870 nM). This compound is structurally dissimilar to known JH agonists and synthetically easy to access; therefore, it is a promising starting point for further structure optimization.

収録刊行物

• 日本農薬学会誌（Ｊｏｕｒｎａｌ　ｏｆ　Ｐｅｓｔｉｃｉｄｅ　Ｓｃｉｅｎｃｅ）

  日本農薬学会誌（Ｊｏｕｒｎａｌ　ｏｆ　Ｐｅｓｔｉｃｉｄｅ　Ｓｃｉｅｎｃｅ） 46 (1), 68-74, 2021-02-20

  日本農薬学会

キーワード

• juvenile hormone agonist
• methoprene-tolerant
• virtual screening
• molecular dynamics
• MM/PBSA
• <i>Drosophila melanogaster</i>

詳細情報

• CRID: 1390005822570643840
• NII論文ID: 130007992095
• NII書誌ID: AA11818622
• DOI: 10.1584/jpestics.d20-074
• ISSN: 13490923
• ISSN: 03851559
• ISSN: 1348589X
• HANDLE: 2433/276831
• NDL書誌ID: 031472823
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I031472823
• Web Site: https://www.jstage.jst.go.jp/article/jpestics/46/1/46_D20-074/_pdf
• 本文言語コード: en
• データソース種別:
  • JaLC
  • IRDB
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可