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Design and activity validation of GABA-gated chloride channels allosteric modulators based on computational biology.

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Title: Design and activity validation of GABA-gated chloride channels allosteric modulators based on computational biology.
Authors: Yang, Siyi1 (AUTHOR), Gao, Shuang1,2 (AUTHOR), Li, Tiansong1 (AUTHOR), Bi, Jinghu1 (AUTHOR), Fu, Ying1,2 (AUTHOR) fuying@neau.edu.cn, Ye, Fei1,2 (AUTHOR) yefei@neau.edu.cn
Source: Pesticide Biochemistry & Physiology. Apr2026, Vol. 219, pN.PAG-N.PAG. 1p.
Subject Terms: *Insecticides, *Insecticidal plants, GABA receptors, Computational biology, Drug design, Molecular docking, Diamondback moth, Molecular dynamics
Abstract: Ionotropic γ - aminobutyric acid (GABA) receptors are the predominant inhibitory neurotransmitter receptors in the insect nervous system and serve as critical targets for insecticides. Meta - diamide insecticides exert their effects by binding to GABA receptors, inhibiting chloride ion influx, causing insects excited and convulsed, ultimately leading to death. To develop novel insecticides with enhanced bioactivity, this study selected broflanilide as a lead compound and employed scaffold hopping and substituent modification strategies to design and synthesize a series of meta - diamide derivatives containing cycloalkanes. Preliminary assays indicated that some compounds exhibited promising insecticidal effects against Plutella xylostella. Compound T-10 displayed median lethal concentration (LC 50) value of 0.004 mg/L, which was comparable to broflanilide (LC 50 = 0.009 mg/L). Molecular docking confirmed that descyclopropylmethyl -T-10 and desmethyl - broflanilide exhibited similar binding modes at the active site of the GABA receptor in Drosophila melanogaster. Molecular dynamics simulations further validated the stable binding of descyclopropylmethyl -T-10 to the GABA receptor, demonstrating its strong inhibitory effect. Density Functional Theory (DFT) calculation indicated a negative correlation between the HOMO - LUMO gap values (ΔE) of desmethyl - broflanilide and descyclopropylmethyl -T-10 and their bioassay results. This study provides a promising compound structure as a novel meta - diamide lead compound to control Plutella xylostella. [Display omitted] • Meta-diamide insecticides were developed via scaffold hopping and computation. • Target compound shared the same mechanism of action as meta-diamide insecticides. • A structural framework was provided for designing green meta-diamide insecticides. [ABSTRACT FROM AUTHOR]
Copyright of Pesticide Biochemistry & Physiology is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: Design and activity validation of GABA-gated chloride channels allosteric modulators based on computational biology.
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  Data: <searchLink fieldCode="AR" term="%22Yang%2C+Siyi%22">Yang, Siyi</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gao%2C+Shuang%22">Gao, Shuang</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Tiansong%22">Li, Tiansong</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bi%2C+Jinghu%22">Bi, Jinghu</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fu%2C+Ying%22">Fu, Ying</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> fuying@neau.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Ye%2C+Fei%22">Ye, Fei</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> yefei@neau.edu.cn</i>
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  Data: <searchLink fieldCode="JN" term="%22Pesticide+Biochemistry+%26+Physiology%22">Pesticide Biochemistry & Physiology</searchLink>. Apr2026, Vol. 219, pN.PAG-N.PAG. 1p.
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: *<searchLink fieldCode="DE" term="%22Insecticides%22">Insecticides</searchLink><br />*<searchLink fieldCode="DE" term="%22Insecticidal+plants%22">Insecticidal plants</searchLink><br /><searchLink fieldCode="DE" term="%22GABA+receptors%22">GABA receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Computational+biology%22">Computational biology</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+design%22">Drug design</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+docking%22">Molecular docking</searchLink><br /><searchLink fieldCode="DE" term="%22Diamondback+moth%22">Diamondback moth</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+dynamics%22">Molecular dynamics</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Ionotropic γ - aminobutyric acid (GABA) receptors are the predominant inhibitory neurotransmitter receptors in the insect nervous system and serve as critical targets for insecticides. Meta - diamide insecticides exert their effects by binding to GABA receptors, inhibiting chloride ion influx, causing insects excited and convulsed, ultimately leading to death. To develop novel insecticides with enhanced bioactivity, this study selected broflanilide as a lead compound and employed scaffold hopping and substituent modification strategies to design and synthesize a series of meta - diamide derivatives containing cycloalkanes. Preliminary assays indicated that some compounds exhibited promising insecticidal effects against Plutella xylostella. Compound T-10 displayed median lethal concentration (LC 50) value of 0.004 mg/L, which was comparable to broflanilide (LC 50 = 0.009 mg/L). Molecular docking confirmed that descyclopropylmethyl -T-10 and desmethyl - broflanilide exhibited similar binding modes at the active site of the GABA receptor in Drosophila melanogaster. Molecular dynamics simulations further validated the stable binding of descyclopropylmethyl -T-10 to the GABA receptor, demonstrating its strong inhibitory effect. Density Functional Theory (DFT) calculation indicated a negative correlation between the HOMO - LUMO gap values (ΔE) of desmethyl - broflanilide and descyclopropylmethyl -T-10 and their bioassay results. This study provides a promising compound structure as a novel meta - diamide lead compound to control Plutella xylostella. [Display omitted] • Meta-diamide insecticides were developed via scaffold hopping and computation. • Target compound shared the same mechanism of action as meta-diamide insecticides. • A structural framework was provided for designing green meta-diamide insecticides. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Pesticide Biochemistry & Physiology is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/j.pestbp.2026.107002
    Languages:
      – Code: eng
        Text: English
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      Pagination:
        PageCount: 1
        StartPage: N.PAG
    Subjects:
      – SubjectFull: Insecticides
        Type: general
      – SubjectFull: Insecticidal plants
        Type: general
      – SubjectFull: GABA receptors
        Type: general
      – SubjectFull: Computational biology
        Type: general
      – SubjectFull: Drug design
        Type: general
      – SubjectFull: Molecular docking
        Type: general
      – SubjectFull: Diamondback moth
        Type: general
      – SubjectFull: Molecular dynamics
        Type: general
    Titles:
      – TitleFull: Design and activity validation of GABA-gated chloride channels allosteric modulators based on computational biology.
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            NameFull: Yang, Siyi
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            NameFull: Gao, Shuang
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            NameFull: Li, Tiansong
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            NameFull: Bi, Jinghu
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            NameFull: Fu, Ying
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            – D: 01
              M: 04
              Text: Apr2026
              Type: published
              Y: 2026
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              Value: 00483575
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              Value: 219
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            – TitleFull: Pesticide Biochemistry & Physiology
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