Understanding the interaction modes and reactivity of trimedoxime toward MmAChE inhibited by nerve agents: theoretical and experimental aspects
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , |
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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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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1815439367302283264 |