Novel Anthranilic Diamide Scaffolds Containing N-Substituted Phenylpyrazole as Potential Ryanodine Receptor Activators.
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 (1)H NMR, (13)C 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 ([Ca(2+)]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.
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Jing-Bo
JB
Liu
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Yu-Xin
YX
Li
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Xiu-Lan
XL
Zhang
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Xue-Wen
XW
Hua
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Chang-Chun
CC
Wu
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Wei
W
Wei
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Ying-Ying
YY
Wan
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Dan-Dan
DD
Cheng
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Li-Xia
LX
Xiong
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Na
N
Yang
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Hai-Bin
HB
Song
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, China.
Zheng-Ming
ZM
Li
D000818:Animals; D002120:Calcium Channel Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D003958:Diamide; D015195:Drug Design; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007555:Isoxazoles / Q000737:chemistry*; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D015394:Molecular Structure; D009036:Moths / Q000187:drug effects / Q000254:growth & development; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D002120:Calcium Channel Agonists; D019476:Insect Proteins; D007306:Insecticides; D007555:Isoxazoles; D019837:Ryanodine Receptor Calcium Release Channel; D003958:Diamide; C033962:anthranil
N-substituted phenylpyrazole; calcium channel; chlorine; insecticidal activity; nitro