Análises In Silico Por 2D e 3D-QSAR e Simulações de Dinâmica Molecular em Derivados de Fosfopirazina e Fosfoguanidina na Projeção de Potenciais Inibidores da AChE da Mosca-Branca (Bemisia Tabaci)

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Data
2024-01-08
Autores
Souza, Fernanda Fernandes de
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Universidade Federal do Espírito Santo
Resumo
The acetylcholinesterase (AChE) is a significant molecular target in insecticide development, but it is also found in the human body, requiring the characterization of the inhibitory profile of compounds for achieving selectivity. In this study, we employed molecular modeling and 3D-QSAR approaches to identify new AChE inhibitors for Bemisia tabaci, a common agricultural pest in tropical and subtropical crops. Molecular docking simulations and quantitative structure-activity relationship (QSAR) analysis were conducted to identify compounds with potential inhibitory activity and develop a predictive model for the activity of these new compounds. The validated model demonstrated good predictive performance with q²= 0.953 and r²= 0.999. We used the model to screen newly substituted molecules by selecting chemical groups in favorable regions of the most active molecule in the dataset, leading to the identification of promising candidates, including FS168. Molecular dynamics simulations with FS168 in complex with B. tabaci AChE revealed the stabilization and interaction of important catalytic amino acids, indicating a possible inhibition mechanism, along with a binding affinity of ΔG= -30.49 kcal/mol. The results highlight the potential of combining molecular modeling and 3D-QSAR approaches for discovering new potential AChE inhibitors for Bemisia tabaci as selective agrochemicals.
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Bemisia tabaci , Acetilcolinesterase , Organofosforados , QSAR , dinâmica molecular
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