Abstract:
To develop highly efficient and structurally novel insect growth regulators, 20 1-phenyl-5-amino pyrazoles were designed and synthesized using ecdysteroid receptor (EcR) as the target and
I7 (
N-(4-cyano-1-phenyl-1
H-pyrazol-5-yl)-2-phenylacetamide), a highly active compound discovered by our group, as a lead. All synthesized structures were confirmed by
1H NMR,
13C NMR and HRMS. The insecticidal activity of the compounds showed that the lethality of compounds
M10,
M17 and
M18 was more than 20% higher than that of lead compound
I7 (60%) at a concentration of 250 mg/L. Compound
M10 was the most active, exhibiting a lethality rate of 60% at 125 mg/L, which is slightly lower than that of the commercial tebufenozide (70%), and
Plutella xylostella treated with this compound showed typical symptoms of ecdysteroid analogue poisoning. The results of the target binding activity of
P. xylostella EcR(
PxEcR) showed that the compounds
M2,
M6,
M9,
M12,
M13,
M15 and
M20 were better than that of compound
I7, and that the target binding activity of compound
M15 (IC
50(
PxEcR) = 2.02 μmol/L) was 11.5 times higher than that of compound
I7 (IC
50(
PxEcR) = 23.21 μmol/L). The binding mechanism between compounds
I7,
M10,
M15 and EcR receptor was further analyzed by molecular docking and molecular dynamics simulation, which will provide guidance for the further research on insect growth regulators targeting EcR.