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Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/Modulator Insecticides.

Publication ,  Journal Article
Zhang, J; Hao, W; Zhorov, BS; Dong, K; Jiang, D
Published in: Journal of agricultural and food chemistry
July 2019

Indoxacarb, a commercialized oxadiazine insecticide, nearly irreversibly blocks open/inactivated, but not resting sodium channels. The structure-activity relationships showed that the substituents at the position of the chiral atom in the oxadiazine ring are very important to the biological activity of oxadiazine insecticide. Here we synthesized a series of tricyclic oxadiazine 4a-methyl ester derivatives. The chiral atom in the oxadiazine ring has been epimerized and substituted with either pyrethric acid or cinnamic acid derivatives. Benzene ring in the tricyclic moiety was substituted with a chlorine, fluorine, or bromine atom, and nitrogen-linked benzene ring was substituted with a trifluoromethyl or trifluoromethoxy group. Toxicity of these compounds against Spodoptera litura F. was evaluated. Diastereoisomers of most toxic compounds J7 and J9 with pyrethric acid moiety were separated by flash column chromatography. The more polar diastereoisomers, J7-L-Rf and J9-L-Rf, and compounds J24 and J26 with cinnamic acid moiety exhibited highest insecticidal activities. We further used Monte Carlo energy minimizations to dock compound J7 and J24 in the NavMs-based homology model of the open cockroach sodium channel. In the low-energy binding modes, the compound interacted with residues in the inner pore and domain interfaces, which previously were proposed to contribute to receptors of pyrethroids and sodium channel blocker insecticides. Our results define compound J7 and J24 as a potentially useful optimized hit for the development of multiple sites sodium channel blocker or modulator.

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Published In

Journal of agricultural and food chemistry

DOI

EISSN

1520-5118

ISSN

0021-8561

Publication Date

July 2019

Volume

67

Issue

28

Start / End Page

7793 / 7809

Related Subject Headings

  • Structure-Activity Relationship
  • Spodoptera
  • Sodium Channels
  • Sodium Channel Blockers
  • Oxazines
  • Models, Molecular
  • Insecticides
  • Insect Proteins
  • Food Science
  • Esters
 

Citation

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Zhang, J., Hao, W., Zhorov, B. S., Dong, K., & Jiang, D. (2019). Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/Modulator Insecticides. Journal of Agricultural and Food Chemistry, 67(28), 7793–7809. https://doi.org/10.1021/acs.jafc.9b00826
Zhang, Jianqiang, Wenbo Hao, Boris S. Zhorov, Ke Dong, and Dingxin Jiang. “Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/Modulator Insecticides.Journal of Agricultural and Food Chemistry 67, no. 28 (July 2019): 7793–7809. https://doi.org/10.1021/acs.jafc.9b00826.
Zhang J, Hao W, Zhorov BS, Dong K, Jiang D. Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/Modulator Insecticides. Journal of agricultural and food chemistry. 2019 Jul;67(28):7793–809.
Zhang, Jianqiang, et al. “Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/Modulator Insecticides.Journal of Agricultural and Food Chemistry, vol. 67, no. 28, July 2019, pp. 7793–809. Epmc, doi:10.1021/acs.jafc.9b00826.
Zhang J, Hao W, Zhorov BS, Dong K, Jiang D. Discovery of a Novel Series of Tricyclic Oxadiazine 4a-Methyl Esters Based on Indoxacarb as Potential Sodium Channel Blocker/Modulator Insecticides. Journal of agricultural and food chemistry. 2019 Jul;67(28):7793–7809.
Journal cover image

Published In

Journal of agricultural and food chemistry

DOI

EISSN

1520-5118

ISSN

0021-8561

Publication Date

July 2019

Volume

67

Issue

28

Start / End Page

7793 / 7809

Related Subject Headings

  • Structure-Activity Relationship
  • Spodoptera
  • Sodium Channels
  • Sodium Channel Blockers
  • Oxazines
  • Models, Molecular
  • Insecticides
  • Insect Proteins
  • Food Science
  • Esters