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dc.creatorMladenović, Milan P.
dc.creatorArsić, Biljana B.
dc.creatorStanković, Nevena M.
dc.creatorMihović, Nezrina
dc.creatorRagno, Rino
dc.creatorRegan, Andrew C.
dc.creatorMilićević, Jelena S.
dc.creatorTrtić-Petrović, Tatjana M.
dc.creatorMicić, Ružica J.
dc.date.accessioned2018-10-17T08:06:40Z
dc.date.available2018-10-17T08:06:40Z
dc.date.issued2018
dc.identifier.issn1420-3049 (print)
dc.identifier.urihttp://www.mdpi.com/1420-3049/23/9/2192
dc.identifier.urihttp://vinar.vin.bg.ac.rs/handle/123456789/7862
dc.description.abstractCommercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either mAChE or hAChE, to predict the listed pesticides’ binding modes. Calculated energies of global minima (Eglob_min) and free energies of binding (∆Gbinding) were correlated with the pesticides’ acute toxicities (i.e., the LD50 values) against mice, as well to generate the model that could predict the LD50s against humans. Although for most of the pesticides the low Eglob_min correlates with the high acute toxicity, it is the ∆Gbinding that conditions the LD50 values for all the evaluated pesticides. Derived pLD50 = f(∆Gbinding) mAChE model may predict the pLD50 against hAChE, too. The hAChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/45006/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/174007/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/43004/RS//
dc.relationSapienza Università di Roma (C26A15RT82)
dc.relationSapienza Università di Roma (C26A15J3BB)
dc.rightsopenAccess
dc.sourceMolecules
dc.subjectpesticides
dc.subjectAChEen
dc.subjectconformational analysisen
dc.subjectQSARen
dc.subjectmolecular dockingen
dc.subjectmolecular dynamicsen
dc.subjectquantum-chemical studiesen
dc.subjectconcentration-dependent kinetic studiesen
dc.titleThe Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitroen
dc.typearticleen
dc.rights.licenseBY
dcterms.abstractМиховић, Незрина; Тртић-Петровић, Татјана М.; Мицић, Ружица Ј.; Милићевић, Јелена С.; Реган, Aндреw Ц.; Младеновић, Милан П.; Aрсић, Биљана Б.; Станковић, Невена М.; Рагно, Рино;
dc.rights.holder© 2018 by the authors
dc.citation.volume23
dc.citation.issue9
dc.citation.spage2192
dc.identifier.wos000447365100103
dc.identifier.doi10.3390/molecules23092192
dc.identifier.pmid30200244
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-85052651030
dc.identifier.fulltexthttp://vinar.vin.bg.ac.rs//bitstream/id/10546/molecules-23-02192.pdf


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