Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Research, Society and Development |
Texto Completo: | https://rsdjournal.org/index.php/rsd/article/view/40292 |
Resumo: | Objective: to analyze the interaction of cannabidiol (CBD) with Nav1.7 and compare it with carbamazepine (CBZ) through molecular docking. Methodology: a quantitative and experimental research, of the in silico type, which used CBD (CID: 644019) and CBZ (CID: 2554, standard drug blocker), anticonvulsant used in chronic pain, on the Nav1.7 channel (PDB: 6N4I), as target protein. Docking simulations were obtained using the Dockthor®, analyzed and visualized using UCSF Chimera®. The results of the CBD and CBZ simulations were arranged in order of highest affinity with the channel protein. The affinities scores were compared using the Student t-test in the GraphPad Prism®, where p values p < 0.05 were considered significant. Results: 1,000,000 evaluations of the possible interactions of CBD and CBZ with Nav1.7 were carried out, which the best three with the lowest binding energy (kcal/mol) were selected. The predicted binding affinity scores of Nav1.7 protein and CBD, and CBZ were - 8.61 ± 0.008 and - 8.47 ± 0.27, respectively. Comparing these values, it was noted that affinities did not difference significant (p = 0.31), which is reflected in the similar positions of each one in the channel and possible therapeutic potency. CBD is hydrogen bonded to THR180 residue with the distance of 1.86 Å. Conclusions: cannabidiol binds to Nav1.7, being able to block it. These data support the clinical use of cannabidiol as an analgesic through the neuronal inhibitory pathway. |
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Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 Prospección farmacológica de la acción analgésica del cannabidiol a través del acoplamiento molecular: interacciones con el canal de sodio dependiente de voltaje Nav1.7Prospecção farmacológica da ação analgésica do canabidiol através de docking molecular: interações com o canal de sódio dependente de voltagem Nav1.7CannabidiolAnalgesicDrug designVoltage-gated sodium channel Nav1.7.AnalgésicoCannabidiolDiseño de fármacosCanales de sodio activados por voltaje Nav1.7.CanabidiolAnalgésicoModelagem de drogasCanal de sódio dependente de voltagem Nav1.7.Objective: to analyze the interaction of cannabidiol (CBD) with Nav1.7 and compare it with carbamazepine (CBZ) through molecular docking. Methodology: a quantitative and experimental research, of the in silico type, which used CBD (CID: 644019) and CBZ (CID: 2554, standard drug blocker), anticonvulsant used in chronic pain, on the Nav1.7 channel (PDB: 6N4I), as target protein. Docking simulations were obtained using the Dockthor®, analyzed and visualized using UCSF Chimera®. The results of the CBD and CBZ simulations were arranged in order of highest affinity with the channel protein. The affinities scores were compared using the Student t-test in the GraphPad Prism®, where p values p < 0.05 were considered significant. Results: 1,000,000 evaluations of the possible interactions of CBD and CBZ with Nav1.7 were carried out, which the best three with the lowest binding energy (kcal/mol) were selected. The predicted binding affinity scores of Nav1.7 protein and CBD, and CBZ were - 8.61 ± 0.008 and - 8.47 ± 0.27, respectively. Comparing these values, it was noted that affinities did not difference significant (p = 0.31), which is reflected in the similar positions of each one in the channel and possible therapeutic potency. CBD is hydrogen bonded to THR180 residue with the distance of 1.86 Å. Conclusions: cannabidiol binds to Nav1.7, being able to block it. These data support the clinical use of cannabidiol as an analgesic through the neuronal inhibitory pathway.Objetivo: analizar la interacción del canabidiol (CBD) con Nav1.7 y compararla con la carbamazepina (CBZ) a través del acoplamiento molecular. Metodologia: trata-se de uma pesquisa quantitativa e experimental, do tipo in silico, que utilizou como substâncias testes, o CBD (CID: 644019) e a carbamazepina (CID: 2554, bloqueador controle), anticonvulsivante padrão used na dor crônica, sobre o canal Nav1.7 (PDB: 6N4I), como proteína alvo. Los experimentos de acoplamiento de foraminíferos moleculares obtenidos mediante el portal en línea Dockthor®, analizados y visualizados por UCSF Chimera®. Os resultados das simulações do CBD y da CBZ foram estabelecidos ordem of maior afinidade com a protein canal. Como afinidades por el uso de la prueba “t” de Student en el programa GraphPad Prism®, los valores de p < 0,05 fueron considerados significativos. Resultados: foram realizó 1.000,000 avaliações das possíveis interações do CDB e CBZ no Nav1.7, destas as três melhores, com menor energia de ligação (kcal/mol) ou melhor afinidade, foram selecionadas. O CDB y CBZ presentan una afinidad de - 8,61 ± 0,008 e - 8,47 ± 0,27 kcal/mol, respectivamente. Comparando-se esses valores, notou-se que não houve diferença estatística significante (p = 0,31), o que se reflete posiciones similares de cada um no canal e também possível potência terapêutica. El CBD hizo un enlace de hidrógeno con el residuo THR180 con una distancia de 1,86 Å. Conclusiones: o canabidiol se liga ao Nav1.7, sendo capaz de bloquear-lo. Estos dados son fundamentales o el uso clínico del canabidiol como analgésico pela vía inibitória neuronal. Objetivo: analisar a interação do canabidiol (CBD) com Nav1.7 e comparar com a carbamazepina (CBZ) através de docking molecular. Metodologia: trata-se de uma pesquisa quantitativa e experimental, do tipo in silico, que utilizou como substâncias testes, o CBD (CID: 644019) e a carbamazepina (CID: 2554, bloqueador controle), anticonvulsivante padrão utilizado na dor crônica, sobre o canal Nav1.7 (PDB: 6N4I), como proteína alvo. Os experimentos de docking molecular foram obtidos usando o portal online Dockthor®, analisados e visualizados pelo UCSF Chimera®. Os resultados das simulações do CBD e da CBZ foram estabelecidos em ordem de maior afinidade com a proteína canal. As afinidades foram comparadas utilizando teste “t” de Student no programa GraphPad Prism®, onde valores de p < 0,05 foram considerados significantes. Resultados: foram realizadas 1.000,000 avaliações das possíveis interações do CDB e CBZ no Nav1.7, destas as três melhores, com menor energia de ligação (kcal/mol) ou melhor afinidade, foram selecionadas. O CBD e CBZ apresentaram afinidade de - 8,61 ± 0,008 e - 8,47 ± 0,27 kcal/mol, respectivamente. Comparando-se esses valores, notou-se que não houve diferença estatística significante (p = 0,31), o que se reflete posicionamentos similares de cada um no canal e também possível potência terapêutica. O CBD fez uma ligação de hidrogênio com o resíduo THR180 com uma distância de 1,86 Å. Conclusões: o canabidiol se liga ao Nav1.7, sendo capaz de bloqueá-lo. Estes dados fundamentam o uso clínico do canabidiol como analgésico pela via inibitória neuronal.Research, Society and Development2023-02-18info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://rsdjournal.org/index.php/rsd/article/view/4029210.33448/rsd-v12i3.40292Research, Society and Development; Vol. 12 No. 3; e30340292Research, Society and Development; Vol. 12 Núm. 3; e30340292Research, Society and Development; v. 12 n. 3; e303402922525-3409reponame:Research, Society and Developmentinstname:Universidade Federal de Itajubá (UNIFEI)instacron:UNIFEIenghttps://rsdjournal.org/index.php/rsd/article/view/40292/33012Copyright (c) 2023 Gidelson José da Silva Júnior; Gisele Evelin de Jesus Arruda; Nayara Barbosa Dantas Lira; Neuton Barbosa Dantas Lira; Alessandra Emertice de Almeida Costa; Cintia Yoko Morioka; Joelmir Lucena Veiga da Silvahttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessSilva Júnior, Gidelson José daArruda, Gisele Evelin de JesusLira, Nayara Barbosa DantasLira, Neuton Barbosa DantasCosta, Alessandra Emertice de AlmeidaMorioka, Cintia YokoSilva, Joelmir Lucena Veiga da2023-03-23T08:33:38Zoai:ojs.pkp.sfu.ca:article/40292Revistahttps://rsdjournal.org/index.php/rsd/indexPUBhttps://rsdjournal.org/index.php/rsd/oairsd.articles@gmail.com2525-34092525-3409opendoar:2023-03-23T08:33:38Research, Society and Development - Universidade Federal de Itajubá (UNIFEI)false |
dc.title.none.fl_str_mv |
Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 Prospección farmacológica de la acción analgésica del cannabidiol a través del acoplamiento molecular: interacciones con el canal de sodio dependiente de voltaje Nav1.7 Prospecção farmacológica da ação analgésica do canabidiol através de docking molecular: interações com o canal de sódio dependente de voltagem Nav1.7 |
title |
Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 |
spellingShingle |
Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 Silva Júnior, Gidelson José da Cannabidiol Analgesic Drug design Voltage-gated sodium channel Nav1.7. Analgésico Cannabidiol Diseño de fármacos Canales de sodio activados por voltaje Nav1.7. Canabidiol Analgésico Modelagem de drogas Canal de sódio dependente de voltagem Nav1.7. |
title_short |
Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 |
title_full |
Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 |
title_fullStr |
Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 |
title_full_unstemmed |
Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 |
title_sort |
Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7 |
author |
Silva Júnior, Gidelson José da |
author_facet |
Silva Júnior, Gidelson José da Arruda, Gisele Evelin de Jesus Lira, Nayara Barbosa Dantas Lira, Neuton Barbosa Dantas Costa, Alessandra Emertice de Almeida Morioka, Cintia Yoko Silva, Joelmir Lucena Veiga da |
author_role |
author |
author2 |
Arruda, Gisele Evelin de Jesus Lira, Nayara Barbosa Dantas Lira, Neuton Barbosa Dantas Costa, Alessandra Emertice de Almeida Morioka, Cintia Yoko Silva, Joelmir Lucena Veiga da |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Silva Júnior, Gidelson José da Arruda, Gisele Evelin de Jesus Lira, Nayara Barbosa Dantas Lira, Neuton Barbosa Dantas Costa, Alessandra Emertice de Almeida Morioka, Cintia Yoko Silva, Joelmir Lucena Veiga da |
dc.subject.por.fl_str_mv |
Cannabidiol Analgesic Drug design Voltage-gated sodium channel Nav1.7. Analgésico Cannabidiol Diseño de fármacos Canales de sodio activados por voltaje Nav1.7. Canabidiol Analgésico Modelagem de drogas Canal de sódio dependente de voltagem Nav1.7. |
topic |
Cannabidiol Analgesic Drug design Voltage-gated sodium channel Nav1.7. Analgésico Cannabidiol Diseño de fármacos Canales de sodio activados por voltaje Nav1.7. Canabidiol Analgésico Modelagem de drogas Canal de sódio dependente de voltagem Nav1.7. |
description |
Objective: to analyze the interaction of cannabidiol (CBD) with Nav1.7 and compare it with carbamazepine (CBZ) through molecular docking. Methodology: a quantitative and experimental research, of the in silico type, which used CBD (CID: 644019) and CBZ (CID: 2554, standard drug blocker), anticonvulsant used in chronic pain, on the Nav1.7 channel (PDB: 6N4I), as target protein. Docking simulations were obtained using the Dockthor®, analyzed and visualized using UCSF Chimera®. The results of the CBD and CBZ simulations were arranged in order of highest affinity with the channel protein. The affinities scores were compared using the Student t-test in the GraphPad Prism®, where p values p < 0.05 were considered significant. Results: 1,000,000 evaluations of the possible interactions of CBD and CBZ with Nav1.7 were carried out, which the best three with the lowest binding energy (kcal/mol) were selected. The predicted binding affinity scores of Nav1.7 protein and CBD, and CBZ were - 8.61 ± 0.008 and - 8.47 ± 0.27, respectively. Comparing these values, it was noted that affinities did not difference significant (p = 0.31), which is reflected in the similar positions of each one in the channel and possible therapeutic potency. CBD is hydrogen bonded to THR180 residue with the distance of 1.86 Å. Conclusions: cannabidiol binds to Nav1.7, being able to block it. These data support the clinical use of cannabidiol as an analgesic through the neuronal inhibitory pathway. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-02-18 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/40292 10.33448/rsd-v12i3.40292 |
url |
https://rsdjournal.org/index.php/rsd/article/view/40292 |
identifier_str_mv |
10.33448/rsd-v12i3.40292 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://rsdjournal.org/index.php/rsd/article/view/40292/33012 |
dc.rights.driver.fl_str_mv |
https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
https://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 |
Research, Society and Development |
publisher.none.fl_str_mv |
Research, Society and Development |
dc.source.none.fl_str_mv |
Research, Society and Development; Vol. 12 No. 3; e30340292 Research, Society and Development; Vol. 12 Núm. 3; e30340292 Research, Society and Development; v. 12 n. 3; e30340292 2525-3409 reponame:Research, Society and Development instname:Universidade Federal de Itajubá (UNIFEI) instacron:UNIFEI |
instname_str |
Universidade Federal de Itajubá (UNIFEI) |
instacron_str |
UNIFEI |
institution |
UNIFEI |
reponame_str |
Research, Society and Development |
collection |
Research, Society and Development |
repository.name.fl_str_mv |
Research, Society and Development - Universidade Federal de Itajubá (UNIFEI) |
repository.mail.fl_str_mv |
rsd.articles@gmail.com |
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1797052618452762624 |