Improving Insecticidal Activity of Chlorantraniliprole by Replacing the Chloropyridinyl Moiety with a Substituted Cyanophenyl Group

Abstract

Insect ryanodine receptors (RyRs) are molecular targets of the anthranilic diamide insecticides. In the present study, a new series of anthranilic diamides containing a cyanophenyl pyrazole moiety were rationally designed by active-fragment assembly and computer-aided design using the 3D structure of Plutella xylostella RyRs as a receptor and chlorantraniliprole as a ligand. Most of the titled compounds showed good toxicity against Mythimna separate, P. xylostella, and Spodoptera frugiperda. Compounds CN06, CN11, and CN16 with corresponding LC50 values of 0.15, 0.29, and 0.52 mg·L–1, respectively, against M. separate showed comparable activity to that of chlorantraniliprole (0.13 mg·L–1). Surprisingly, CN06, CN11, and CN16 with corresponding LC50 values of 1.6 × 10–5, 3.0 × 10–5, and 2.8 × 10–5 mg·L–1, respectively, against P. xylostella were at least 5-fold more active than chlorantraniliprole (1.5 × 10–4 mg·L–1). In the case of S. frugiperda, CN06, CN11, and CN16 had good potency but lower than chlorantraniliprole in terms of LC50 values (0.58, 0.54, and 0.56 mg·L–1 versus 0.31 mg·L–1). Molecular docking of CN06 and chlorantraniliprole to P. xylostella RyRs validated the molecular design, and the calcium imaging technique further proved the potential target of CN06 as RyRs. Compounds CN06, CN11, and CN16 could be more effective than chlorantraniliprole in targeting the resistant RyR mutants of S. frugiperda (G4891E, I4734M) through the binding mode and energy obtained by molecular docking. Density functional theory calculations (DFT) and electrostatic potential (ESP) studies gave the structure–activity relationship. Compounds CN06, CN11, and CN16 could be used as potent insecticide leads for further optimization.

Anthranilic Diamides Containing Monofluoroalkene Amide Linkers as Potential Insect RyR Activators: Design, Synthesis, Bio-evaluation, and Computational Study

“…Calcium imaging-based studies were conducted as described in the reported literature. 39,41 Isolation of M. separata Neurons. M. separata were initially obtained from shallot fields in Tianjin, China, and reared indoors in climatic chambers on an agar-based semisynthetic diet at 27 ± 1 °C, 75 ± 5% relative humidity, and 16:8 h light:dark (LD) photocycle.…”

3D-QSAR Directed Discovery of Novel Halogenated Phenyl 3-Trifluoroethoxypyrazole Containing Ultrahigh Active Insecticidal Anthranilic Diamides

“…The reported mutations such as G4946E and I4790M of P. xylostella RyRs, G4900E and I4743M of Spodoptera exigua RyRs, and G4910E and I4758 M of Chilo suppressalis RyRs were used for locating the homology amino acid mutant sequences of S. frugiperda RyRs, corresponding to G4891E and I4734M of S. frugiperda RyRs, respectively. Therefore, software UCSF chimera 1.16 was used to construct mutant models of S. frugiperda RyRs - E4891 by mutating GLY to GLU, S. frugiperda RyRs - M4734 by mutating ILE to MET . The homology models were refined by YASARA and evaluated by Ramachandran plots (in Supporting Information Figures A and C–F), and the active center (in Supporting Information Figure B) was identified by YASARA.…”

“…Solutions of samples were prepared by the reported method. 24 A susceptible population of M. separata, P. xylostella, S. f rugiperda, and Ostrinia f urnacalis has been reared in the department of bioassay, Nankai University, since 2006, 2010, 2019, and 2010, respectively. The 10 mg•mL −1 mother solution of the test compound was prepared by dissolving 10 mg of a sample in 1 mL of DMF.…”

“…Therefore, software UCSF chimera 1.16 was used to construct mutant models of S. f rugiperda RyRs -E4891 by mutating GLY to GLU, S. f rugiperda RyRs -M4734 by mutating ILE to MET. 24 The homology models were refined by YASARA and evaluated by Ramachandran plots (in Supporting Information Figures A and C−F), and the active center (in Supporting Information Figure B) was identified by YASARA. The docking_run.mcr module of YASARA was used to perform the molecular docking analysis.…”

“…Over a decade, our group have reported some highly active anthranilic diamides such as LJB-12i , ZYY-IIIf , ZY-19a , and YZW-CN06 (Figure ). − Compounds LJB-12i and ZYY-IIIf exhibited comparable activity to chlorantraniliprole against M. separata , but weaker activity against P. xylostella than chlorantraniliprole. In contrast, compound ZY-19a showed better activity against P. xylostella than chlorantraniliprole, but poorer insecticidal activity against M. separata .…”