Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Pest Manag Sci. 2022 Feb;78(2):467-474. doi: 10.1002/ps.6641. Epub 2021 Sep 29.
Photopharmacology is a fast-growing photonics-based technology, which realizes the high-resolution regulation of drugs in time and space through light. The purpose of this research was to introduce photochromic groups into the isoxazoline structure to realize the regulation of γ-Aminobutyric acid receptors (GABARs) targeting insect behavior.
Azobenzene-Fluralaner analogs ABF02, ABF03 and ABF04 have been proven to have larvicidal activity against mosquito larvae. Cis-ABF03 had excellent larvicidal activity against mosquito larvae with a median lethal concentration (LC ) value of 1.63, which was better than that of trans-ABF03 (LC = 3.90). In particular, ABF03 also showed insecticidal activity against Mythimna separata. Further experiments showed that ABF03 (1 μm) induced depolarization of dorsal unpaired median neurons after ultraviolet light irradiation, enhanced affinity to the receptor, and blocked ligand-gated chloride channels of GABARs. ABF03 (1 μm) realized the real-time photoregulation of the behavior of mosquito larvae, which indicated that the synthesized ligand can complete the binding and off-target action of drugs and targets in vivo under the regulation of light.
Azobenzene-Isoxazoline as photopharmacological ligand was synthesized and evaluated for optical control of insect GABARs and behavior for the first time. ABF03 completed the differential regulation of cockroach neurons and the real-time reversible regulation of insect behavior. The establishment of photochromic ligands provides a new strategy for basic and convenience-oriented research on GABARs in invertebrates. © 2021 Society of Chemical Industry.
光药理学是一项快速发展的基于光子学的技术，它通过光实现药物在时间和空间上的高分辨率调控。本研究的目的是将变色基团引入异噁唑啉结构中，实现对昆虫行为的靶向γ-氨基丁酸受体（GABARs）的调控。
已证明偶氮苯-氟虫腈类似物 ABF02、ABF03 和 ABF04 对蚊幼虫具有杀虫活性。顺式-ABF03 对蚊幼虫具有优异的杀虫活性，半数致死浓度（LC ）值为 1.63，优于反式-ABF03（LC = 3.90）。特别是，ABF03 还表现出对粘虫的杀虫活性。进一步的实验表明，ABF03（1μm）在紫外线照射后诱导背侧未配对中神经元去极化，增强与受体的亲和力，并阻断 GABARs 的配体门控氯离子通道。ABF03（1μm）实现了蚊幼虫行为的实时光调控，表明合成的配体可以在光的调节下完成药物和靶标在体内的结合和脱靶作用。
首次合成了偶氮苯-异噁唑啉作为光药理学配体，用于光学控制昆虫 GABARs 和行为。ABF03 完成了蟑螂神经元的差异调控和昆虫行为的实时可逆调控。光致变色配体的建立为研究无脊椎动物 GABARs 的基础和方便导向研究提供了新策略。 © 2021 英国化学学会。
