Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects

Detalhes bibliográficos
Autor(a) principal: Castro, Alexandre A. de
Data de Publicação: 2020
Outros Autores: Polisel, Daniel A., Pereira, Bruna T. L., Cunha, Elaine F. F. da, Kuca, Kamil, Nepovimova, Eugenie, Ramalho, Teodorico C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFLA
Texto Completo: http://repositorio.ufla.br/jspui/handle/1/46665
Resumo: Organophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order to design new antidotes with better efficiency, as well as a greater spectrum of action in the acetylcholinesterase (AChE) reactivation process. With that in mind, in this work, we investigated the behavior of trimedoxime toward the Mus musculus acetylcholinesterase (MmAChE) inhibited by a range of nerve agents, such as chemical weapons. From experimental assays, reactivation percentages were obtained for the reactivation of different AChE–OP complexes. On the other hand, theoretical calculations were performed to assess the differences in interaction modes and the reactivity of trimedoxime within the AChE active site. Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE–VX adduct. From this work, it was revealed that the mechanistic process contributes most to the oxime efficiency than the interaction in the site. In this way, this study is important to better understand the reactivation process through trimedoxime, contributing to the proposal of novel antidotes.
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spelling Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspectsNerve agentsAcetylcholinesteraseTrimedoximeReactivationMechanistic studiesEstudos mecanísticosAgentes nervososAcetilcolinesteraseTrimedoximeReativaçãoOrganophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order to design new antidotes with better efficiency, as well as a greater spectrum of action in the acetylcholinesterase (AChE) reactivation process. With that in mind, in this work, we investigated the behavior of trimedoxime toward the Mus musculus acetylcholinesterase (MmAChE) inhibited by a range of nerve agents, such as chemical weapons. From experimental assays, reactivation percentages were obtained for the reactivation of different AChE–OP complexes. On the other hand, theoretical calculations were performed to assess the differences in interaction modes and the reactivity of trimedoxime within the AChE active site. Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE–VX adduct. From this work, it was revealed that the mechanistic process contributes most to the oxime efficiency than the interaction in the site. In this way, this study is important to better understand the reactivation process through trimedoxime, contributing to the proposal of novel antidotes.MDPI2021-07-06T18:44:29Z2021-07-06T18:44:29Z2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfCASTRO, A. A. de. et al. Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects. International Journal of Molecular Sciences, [S. l.], v. 21, n. 18, 6510, 2020. DOI: 10.3390/ijms21186510.http://repositorio.ufla.br/jspui/handle/1/46665International Journal of Molecular Sciencesreponame:Repositório Institucional da UFLAinstname:Universidade Federal de Lavras (UFLA)instacron:UFLAAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessCastro, Alexandre A. dePolisel, Daniel A.Pereira, Bruna T. L.Cunha, Elaine F. F. daKuca, KamilNepovimova, EugenieRamalho, Teodorico C.eng2021-07-06T18:44:29Zoai:localhost:1/46665Repositório InstitucionalPUBhttp://repositorio.ufla.br/oai/requestnivaldo@ufla.br || repositorio.biblioteca@ufla.bropendoar:2021-07-06T18:44:29Repositório Institucional da UFLA - Universidade Federal de Lavras (UFLA)false
dc.title.none.fl_str_mv Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
title Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
spellingShingle Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
Castro, Alexandre A. de
Nerve agents
Acetylcholinesterase
Trimedoxime
Reactivation
Mechanistic studies
Estudos mecanísticos
Agentes nervosos
Acetilcolinesterase
Trimedoxime
Reativação
title_short Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
title_full Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
title_fullStr Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
title_full_unstemmed Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
title_sort Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
author Castro, Alexandre A. de
author_facet Castro, Alexandre A. de
Polisel, Daniel A.
Pereira, Bruna T. L.
Cunha, Elaine F. F. da
Kuca, Kamil
Nepovimova, Eugenie
Ramalho, Teodorico C.
author_role author
author2 Polisel, Daniel A.
Pereira, Bruna T. L.
Cunha, Elaine F. F. da
Kuca, Kamil
Nepovimova, Eugenie
Ramalho, Teodorico C.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Castro, Alexandre A. de
Polisel, Daniel A.
Pereira, Bruna T. L.
Cunha, Elaine F. F. da
Kuca, Kamil
Nepovimova, Eugenie
Ramalho, Teodorico C.
dc.subject.por.fl_str_mv Nerve agents
Acetylcholinesterase
Trimedoxime
Reactivation
Mechanistic studies
Estudos mecanísticos
Agentes nervosos
Acetilcolinesterase
Trimedoxime
Reativação
topic Nerve agents
Acetylcholinesterase
Trimedoxime
Reactivation
Mechanistic studies
Estudos mecanísticos
Agentes nervosos
Acetilcolinesterase
Trimedoxime
Reativação
description Organophosphorus (OP) compounds are used as both chemical weapons and pesticides. However, these agents are very dangerous and toxic to humans, animals, and the environment. Thus, investigations with reactivators have been deeply developed in order to design new antidotes with better efficiency, as well as a greater spectrum of action in the acetylcholinesterase (AChE) reactivation process. With that in mind, in this work, we investigated the behavior of trimedoxime toward the Mus musculus acetylcholinesterase (MmAChE) inhibited by a range of nerve agents, such as chemical weapons. From experimental assays, reactivation percentages were obtained for the reactivation of different AChE–OP complexes. On the other hand, theoretical calculations were performed to assess the differences in interaction modes and the reactivity of trimedoxime within the AChE active site. Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE–VX adduct. From this work, it was revealed that the mechanistic process contributes most to the oxime efficiency than the interaction in the site. In this way, this study is important to better understand the reactivation process through trimedoxime, contributing to the proposal of novel antidotes.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021-07-06T18:44:29Z
2021-07-06T18:44:29Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv CASTRO, A. A. de. et al. Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects. International Journal of Molecular Sciences, [S. l.], v. 21, n. 18, 6510, 2020. DOI: 10.3390/ijms21186510.
http://repositorio.ufla.br/jspui/handle/1/46665
identifier_str_mv CASTRO, A. A. de. et al. Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects. International Journal of Molecular Sciences, [S. l.], v. 21, n. 18, 6510, 2020. DOI: 10.3390/ijms21186510.
url http://repositorio.ufla.br/jspui/handle/1/46665
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv International Journal of Molecular Sciences
reponame:Repositório Institucional da UFLA
instname:Universidade Federal de Lavras (UFLA)
instacron:UFLA
instname_str Universidade Federal de Lavras (UFLA)
instacron_str UFLA
institution UFLA
reponame_str Repositório Institucional da UFLA
collection Repositório Institucional da UFLA
repository.name.fl_str_mv Repositório Institucional da UFLA - Universidade Federal de Lavras (UFLA)
repository.mail.fl_str_mv nivaldo@ufla.br || repositorio.biblioteca@ufla.br
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