文献类型：期刊文献

英文题名：Light Regulation of Insect Behavior by Azobenzene-modified Flonicamid as Novel Molecular Tools

作者：Sheng, Zhubo[1];Fu, Wen[1,2];Zhang, Hangji[1];Wang, Weiguo[1];Li, Xiaoyan[3];Xu, Zhiping[1];Li, Zhong[1,4];Shao, Xusheng[1,5,6]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Guizhou Univ, Natl Key Lab Green Pesticide, Guiyang 550025, Guizhou, Peoples R China;[3]China Agr Univ, Yantai Inst, Coll Humanities & Econ Management, Yantai 264670, Shandong, Peoples R China;[4]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cell, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[6]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China

年份：2024

卷号：72

期号：48

起止页码：26689

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20244817415879);WOS:【SCI-EXPANDED(收录号:WOS:001360645600001)】；

基金：This work was financially supported by National Natural Science Foundation of China (32472610, 32402439, 32072441), National Key Research and Development Program of China (2018YFD0200100), Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-02-E00037), Tobacco and Health funding program (2022539200340111), Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission), and the project of National Key Laboratory of Green Pesticide/Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University (SKL-GPL-KF-202405).

语种：英文

外文关键词：photopharmacology; azobenzene; photoregulation; Naam; AlphaFold2

摘要：Photopharmacology, an emerging interdisciplinary field, enables precise modulation of target biological activity by employing light-controllable photoswitchable molecules. The research on nicotinamidase (Naam), a recently identified target molecule for pesticides, remains relatively underexplored. Therefore, based on the structure of its inhibitor Flonicamid, we designed and synthesized a series of photopharmacological ligands (FABS) by incorporating a light-controllable azobenzene switch, further investigating their effects on insect behavior and activity. Compound FAB03 exhibited an LC50 value of 32.8 mu M before light exposure and 154 mu M after light exposure against Aedes albopictus, indicating a 4.7-fold difference in activity. Compound FAB05 exhibited an LC50 value of 0.691 mu M before light exposure and 2.85 mu M after light exposure against nymphs (1 day old) of Aphis craccivora, indicating a 4.1-fold difference in activity. Additionally, this series of photopharmacological ligands has successfully achieved light-mediated modulation of locomotor behavior in both Drosophila melanogaster and A. albopictus larvae. Fluorescence staining experiments with A. albopictus larvae were conducted to explore potential modes of action of the drug. Calcium content analysis showed that Flonicamid at 20 mu g/mL significantly caused an inward Ca2+ flux in the ovarian of Spodoptera frugiperda (SF9), and the trans-configurations of the photopharmacological ligands FAB03 and FAB05 also led to a certain increase in the concentration of intracellular Ca2+. AlphaFold2 was employed to predict the three-dimensional structure of Naam, and potential binding modes were elucidated through molecular docking studies.