Mitigating CYP450-Mediated Insecticide Resistance in Malaria Vectors with Cannabis-Derived Synergists: The Potential of Cannabidiol
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Le résumé fourni par la source
Abstract Insecticide resistance in mosquitoes, largely mediated by cytochrome P450 monooxygenases (CYPs), compromises the efficacy of vector control tools. In this study, chemically-wise selected natural extracts and compounds were screened for their CYP inhibition potential. Among 37 tested plant extracts and fractions, a decarboxylated acidic fraction of industrial hemp ( Cannabis sativa Linnaeus var. ‘Futura 75’) emerged as a promising hit, and phytochemical profiling identified cannabidiol (CBD) as its major component (IC₅₀ = 18.37 μM for CYP9K1). CBD was used as a scaffold to generate semisynthetic analogues; of which a piperazinyl analogue outperformed the natural scaffold demonstrating significantly greater potency (IC₅₀ = 2.50 μM for CYP9K1). Docking studies using homology-derived CYP9K1 models also supported a stronger binding affinity of the piperazinyl analogue relative to CBD. Toxicity assays using pyrethroid-resistant Anopheles gambiae Giles adults confirmed that neither CBD nor the piperazinyl analogue had intrinsic toxicity, yet the semisynthetic analogue significantly enhanced deltamethrin efficacy, showing a threefold synergistic effect. The safety profile of the cannabis compounds for non-target organisms was evaluated through human cell line cytotoxicity tests and bee toxicity assays, suggesting low non-target organism toxicity. Our study describes the identification of a plant-derived synergist lead with strong potential as an insecticide additive to combat metabolic resistance in malaria-transmitting mosquitoes.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Mitigating CYP450-Mediated Insecticide Resistance in Malaria Vectors with Cannabis-Derived Synergists: The Potential of Cannabidiol
- Date Crossref
- 11/02/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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National and Kapodistrian University of Athens Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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Foundation for Research and Technology Hellas pays non établi dans la noticeStructure de recherche
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Agricultural University of Athens Department of Crop Science pays non établi dans la noticeUniversité ou école supérieure
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Sapienza University of Rome Department of Drug Chemistry and Technology pays non établi dans la noticeUniversité ou école supérieure
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Athena Research and Innovation Center In Information Communication & Knowledge Technologies pays non établi dans la noticeStructure de recherche
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Institute of Molecular Biology and Biotechnology pays non établi dans la noticeStructure de recherche
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Pharma-Informatics Unit pays non établi dans la noticeInstitution
Department of Pharmacy — National and Kapodistrian University of Athens, Foundation for Research and Technology Hellas et Department of Crop Science — Agricultural University of Athens, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.