Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one derivatives targeting calcium channel

Bioorg Med Chem. 2013 Sep 1;21(17):4968-75. doi: 10.1016/j.bmc.2013.06.060. Epub 2013 Jul 3.

Abstract

A series of compounds containing dihydroquinazolinone moiety was designed and synthesized. Amine bridge part was changed in comparison with known anthranilic diamides insecticides. Their insecticidal activities against oriental armyworm (Mythimna separata) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compounds 5a and 5k showed 80% larvicidal activities against oriental armyworm at the concentration of 5mg/L. The present study also explored the possible effects of target compounds on the high voltage-gated calcium channel and the calcium channels in the endoplasmic reticulum in the central neurons isolated from the third instar larvae of Spodoptera exigua using whole-cell patch clamp and calcium imaging technique. The results showed that compound 5a activated the high voltage-gated calcium channel in the central neurons of S. exigua weakly. The peak currents only increased by 6% of the initial value at the end of the 10-min recording after treated with 0.22μM 5a, while chlorantraniliprole has an opposite effect. The effects of 5a on the intracellular calcium ion concentration ([Ca(2+)]i) in neurons were well investigated. The experimental results indicated that these novel compounds have different mechanism compared with chlorantraniliprole.

Keywords: Anthranilic diamide; Calcium channel; Dihydroquinazolinone; Insecticidal activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / toxicity
  • Calcium Channels / chemistry*
  • Calcium Channels / metabolism
  • Crystallography, X-Ray
  • Insecticides / chemical synthesis*
  • Insecticides / chemistry
  • Insecticides / toxicity
  • Larva / drug effects
  • Larva / physiology
  • Lepidoptera / drug effects
  • Lepidoptera / growth & development
  • Molecular Conformation
  • Neurons / drug effects
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Quinazolinones / chemical synthesis*
  • Quinazolinones / chemistry
  • Quinazolinones / toxicity
  • Spodoptera / drug effects
  • Spodoptera / growth & development
  • Spodoptera / physiology
  • Structure-Activity Relationship

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Insecticides
  • Quinazolinones
  • Calcium