Novel Anthranilic Diamide Scaffolds Containing N‑Substituted Phenylpyrazole as Potential Ryanodine Receptor Activators

• Published in: Journal of agricultural and food chemistry 2016-05, Vol.64 (18), p.3697-3704
• Main Authors: Liu, Jing-Bo, Li, Yu-Xin, Zhang, Xiu-Lan, Hua, Xue-Wen, Wu, Chang-Chun, Wei, Wei, Wan, Ying-Ying, Cheng, Dan-Dan, Xiong, Li-Xia, Yang, Na, Song, Hai-Bin, Li, Zheng-Ming
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channel Agonists - chemical synthesis; Calcium Channel Agonists - chemistry; Calcium Channel Agonists - metabolism; Diamide; Drug Design; Insect Proteins - antagonists & inhibitors; Insect Proteins - chemistry; Insect Proteins - metabolism; Insecticides - chemical synthesis; Insecticides - chemistry; Insecticides - pharmacology; Isoxazoles - chemistry; Larva - drug effects; Larva - growth & development; Molecular Structure; Moths - drug effects; Moths - growth & development; Ryanodine Receptor Calcium Release Channel - chemistry; Ryanodine Receptor Calcium Release Channel - metabolism; Structure-Activity Relationship; X-Ray Diffraction
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.6b00380

To discover potent insecticides targeting ryanodine receptors (RyRs), a series of novel anthranilic diamides analogues (12a–12u) containing N-substituted phenylpyrazole were designed and synthesized. These compounds were characterized by 1H NMR, 13C NMR, and HRMS, and the structure of compound 12u was confirmed by X-ray diffraction. Their insecticidal activities indicated that these compounds displayed moderate to excellent activities. In particular, 12i showed 100 and 37% larvicidal activities against oriental armyworm (Mythimna separata) at 0.25 and 0.05 mg L–1, equivalent to that of chlorantraniliprole (100%, 0.25 mg L–1; and 33%, 0.05 mg L–1). The activity of 12i against diamondback moth (Plutella xylostella) was 95% at 0.05 mg L–1, whereas the control was 100% at 0.05 mg L–1. The calcium-imaging technique experiment results showed that the effects of 12i on the intracellular calcium ion concentration ([Ca2+]i) in neurons were concentration-dependent. After the central neurons of Helicoverpa armigera were dyed by loading with fluo-5N and treated with 12i, the free calcium released in endoplasmic reticulum indicated the target of compound 12i is RyRs or IP3Rs. The activation of RyRs by natural ryanodine completely blocked the calcium release induced by 12i, which indicated that RyRs in the central neurons of H. armigera third-instar larvae is the possible target of compound 12i.