Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel 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), anticonvuls...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Brasil
Institución:Universidade Federal de Itajubá (UNIFEI)
Repositorio:Research, Society and Development
Idioma:inglés
OAI Identifier:oai:ojs.pkp.sfu.ca:article/40292
Acceso en línea:https://rsdjournal.org/index.php/rsd/article/view/40292
Access Level:acceso abierto
Palabra clave:Cannabidiol
Analgesic
Drug design
Voltage-gated sodium channel Nav1.7.
Analgésico
Diseño de fármacos
Canales de sodio activados por voltaje Nav1.7.
Canabidiol
Modelagem de drogas
Canal de sódio dependente de voltagem Nav1.7.
Descripción
Sumario: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.