Direct and indirect toxicity mechanisms of the natural insecticide azadirachtin based on in-silico interactions with tubulin, topoisomerase and DNA

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dc.contributor.authorKutluer, Fatih
dc.contributor.authorÖzkan, Burak
dc.contributor.authorYalçin, Emine
dc.contributor.authorÇavuşoğlu, Kültiğin
dc.date.accessioned2025-01-21T16:27:18Z
dc.date.available2025-01-21T16:27:18Z
dc.date.issued2024
dc.departmentKırıkkale Üniversitesi
dc.description.abstractNatural pesticides, which attract attention with safe properties, pose a threat to many non-target organisms, so their toxic effects should be studied extensively. In this study, the toxic effects of Azadirachtin, a natural insecticide derived from Azadirachta indica, were investigated by in-vivo and in-silico methods. In-vivo toxic effects were determined using the Allium test and bulbs were treated with 5 mg/L (0.5x EC50), 10 mg/L (EC50), and 20 mg/L (2xEC50) Azadirachtin. In the groups treated with Azadirachtin, there was a decline in germination-related parameters and accordingly growth was delayed. This regression may be related to oxidative stress in the plant, and the increase in malondialdehyde and proline levels in Azadirachtin-applied groups confirms oxidative stress. Azadirachtin toxicity increased dose-dependently and the most significant toxic effect was observed in the group administered 20 mg/L Azadirachtin. In this group, the mitotic index decreased by 43.4% and sticky chromosomes, vagrant chromosomes and fragments were detected at rates of 83.1 ± 4.01, 72.7 ± 3.46 and 65.1 ± 3.51, respectively. By comet analysis, it was determined that Azadirachtin caused DNA fragmentation, and tail DNA, which was 0.10 ± 0.32% in the control group, increased to 34.5 ± 1.35% in the Azadirachtin -treated groups. These cytotoxic and genotoxic effects of Azadirachtin may be due to direct interaction with macromolecules as well as induced oxidative stress. Azadirachtin has been found to interact in-silico with alpha-tubulin, beta-tubulin, topoisomerase I and II, and various DNA sequences. Possible deteriorations in macromolecular structure and functions as a result of these interactions may cause cytotoxic and genotoxic effects. These results suggest that natural insecticides may also be unreliable for non-target organisms, and the toxic effects of compounds presented as “natural” should also be investigated. © 2024 Elsevier Ltd
dc.description.sponsorshipmg/L Aza application groups, (10.000–80.000)
dc.identifier.doi10.1016/j.chemosphere.2024.143006
dc.identifier.issn0045-6535
dc.identifier.pmid39098344
dc.identifier.scopus2-s2.0-85200571416
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.chemosphere.2024.143006
dc.identifier.urihttps://hdl.handle.net/20.500.12587/23316
dc.identifier.volume364
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Ltd
dc.relation.ispartofChemosphere
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241229
dc.subjectassessment; Azadirachtin; Comet assay; Molecular docking; Oxidative stress; Toxicity
dc.titleDirect and indirect toxicity mechanisms of the natural insecticide azadirachtin based on in-silico interactions with tubulin, topoisomerase and DNA
dc.typeArticle

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