Hou Qing-Qing, Huang Qiu-Tang, Xu Qi, Zhou Cong, Du Yao-Yao, Ji Yun-Fan, Xu Zhi-Ping, Cheng Jia-Gao, Zhao Chun-Qing, Li Zhong, Shao Xu-Sheng
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy; State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, P. R. China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, P. R. China.
Pest Manag Sci. 2023 Mar;79(3):1086-1093. doi: 10.1002/ps.7279. Epub 2022 Nov 17.
Ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) in an insect is the major inhibitory receptor and is one of the most important targets for insecticides. Due to the high spatiotemporal resolution of GABAR, the photopharmacological ligands acting on it in vertebrates but not insect have been developed.
In this study, two types of photochromic ligands (PCLs) including DTFIPs (DTFIP1 and DTFIP2) and ABFIPs (p-, m-, and o-ABFIP) were synthesized by incorporating photoswitch azobenzene or dithienylethene into fipronil (FIP), which is the antagonist of insect GABAR. Their photomodulation was measured by mosquito larval behavior, and their potential action mechanism was explored by the two-electrode voltage clamp (TEVC) technique in vitro. DTFIP1 and m-ABFIP exhibited the most significant difference of insecticidal activity by about 90- and 5-fold to mosquito larvae between non-irradiated and irradiated formation, respectively, and allowed for optical control of mosquito swimming activity. TEVC assay results indicated that m-ABFIP and DTFIP1 enable optical control over the homomeric LsRDL-type GABAR, which is achieved by regulating the chloride channel of resistance to dieldrin (RDL)-type GABAR by photoisomerization.
Our results suggested that PCLs synthesized from fipronil provide an alternative and precise tool for studying insect ionotropic GABARs and GABA-dependent behavior. © 2022 Society of Chemical Industry.
昆虫中的离子型γ-氨基丁酸（GABA）受体（GABAR）是主要的抑制性受体，也是杀虫剂最重要的作用靶点之一。由于GABAR具有高时空分辨率，已开发出作用于脊椎动物而非昆虫GABAR的光药理学配体。
在本研究中，通过将光开关偶氮苯或二噻吩乙烯引入昆虫GABAR的拮抗剂氟虫腈（FIP）中，合成了两种类型的光致变色配体（PCL），即二噻吩氟虫腈（DTFIP1和DTFIP2）和偶氮氟虫腈（对-、间-和邻-ABFIP）。通过蚊虫幼虫行为测定它们的光调制作用，并通过体外双电极电压钳（TEVC）技术探索其潜在作用机制。DTFIP1和间-ABFIP在未照射和照射状态下对蚊虫幼虫的杀虫活性差异最为显著，分别约为90倍和5倍，并可实现对蚊虫游泳活动的光学控制。TEVC检测结果表明，间-ABFIP和DTFIP1能够对同聚体LsRDL型GABAR进行光学控制，这是通过光异构化调节抗狄氏剂（RDL）型GABAR的氯离子通道实现的。
我们的结果表明，由氟虫腈合成的PCL为研究昆虫离子型GABAR和GABA依赖性行为提供了一种替代且精确的工具。© 2022化学工业协会。
