The inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer

NF-κB contributes to the biosynthesis of various chemokines, cytokines, and enzymes. It plays many crucial roles in the upstream neuroinflammatory pathways. Briefly, the inhibitory IkB subunit is cleaved and phosphorylated by the IKK-α/β enzyme. It leads to the activation and translocation of the NF...

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Autores principales:	Sajad Shahbazi, Tara Zakerali
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	NF-kB translocation Acetylation Phosphorylation IKK-α/β Anti-neuroinflammatory agent Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/441ce3bc39ca4b4c96c5bfeec3f4c704
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spelling	oai:doaj.org-article:441ce3bc39ca4b4c96c5bfeec3f4c7042021-11-30T04:13:41ZThe inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer0753-332210.1016/j.biopha.2021.112471https://doaj.org/article/441ce3bc39ca4b4c96c5bfeec3f4c7042022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221012579https://doaj.org/toc/0753-3322NF-κB contributes to the biosynthesis of various chemokines, cytokines, and enzymes. It plays many crucial roles in the upstream neuroinflammatory pathways. Briefly, the inhibitory IkB subunit is cleaved and phosphorylated by the IKK-α/β enzyme. It leads to the activation and translocation of the NF-κB (p50/p65) complex into the nucleus. Subsequently, the activated NF-κB interacts with the genomic DNA and contributes to expressing various proinflammatory cytokines. In the present study, we developed a novel NF-κB inhibitor encoded (D5) and investigated the efficacy of our druggable compound through several in silico, in vitro, and in situ analysis. The results demonstrated that D5 not only inhibited the mRNA expression of the IKK-α/β enzyme (around 86–96% suppression rate for both cell lines at 12 and 24 h time frames) but also by interacting to the active site of the mentioned kinase (dock score −6.14 and binding energy −23.60 kcal/mol) reduced the level of phosphorylated IkB-α in the cytosol around 96–99% and p65 subunit in the nucleus around 73–90% (among all groups in 12 and 24 h time points). Additionally, the results indicated that D5 suppressed the NF-κB target mRNA levels of TNF-α and IL-6 in a total average of around 92%. Overall, The results demonstrated that D5 in a considerably lower concentration than Dis (0.71 µM vs. 52.73 µM) showed significantly higher inhibitory efficacy on NF-κB translocation approx. 200–300%. The results suggested D5 as a potent NF-κB silencer, but further investigations are required to validate our outcomes.Sajad ShahbaziTara ZakeraliElsevierarticleNF-kB translocationAcetylationPhosphorylationIKK-α/βAnti-neuroinflammatory agentTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112471- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	NF-kB translocation Acetylation Phosphorylation IKK-α/β Anti-neuroinflammatory agent Therapeutics. Pharmacology RM1-950
spellingShingle	NF-kB translocation Acetylation Phosphorylation IKK-α/β Anti-neuroinflammatory agent Therapeutics. Pharmacology RM1-950 Sajad Shahbazi Tara Zakerali The inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer
description	NF-κB contributes to the biosynthesis of various chemokines, cytokines, and enzymes. It plays many crucial roles in the upstream neuroinflammatory pathways. Briefly, the inhibitory IkB subunit is cleaved and phosphorylated by the IKK-α/β enzyme. It leads to the activation and translocation of the NF-κB (p50/p65) complex into the nucleus. Subsequently, the activated NF-κB interacts with the genomic DNA and contributes to expressing various proinflammatory cytokines. In the present study, we developed a novel NF-κB inhibitor encoded (D5) and investigated the efficacy of our druggable compound through several in silico, in vitro, and in situ analysis. The results demonstrated that D5 not only inhibited the mRNA expression of the IKK-α/β enzyme (around 86–96% suppression rate for both cell lines at 12 and 24 h time frames) but also by interacting to the active site of the mentioned kinase (dock score −6.14 and binding energy −23.60 kcal/mol) reduced the level of phosphorylated IkB-α in the cytosol around 96–99% and p65 subunit in the nucleus around 73–90% (among all groups in 12 and 24 h time points). Additionally, the results indicated that D5 suppressed the NF-κB target mRNA levels of TNF-α and IL-6 in a total average of around 92%. Overall, The results demonstrated that D5 in a considerably lower concentration than Dis (0.71 µM vs. 52.73 µM) showed significantly higher inhibitory efficacy on NF-κB translocation approx. 200–300%. The results suggested D5 as a potent NF-κB silencer, but further investigations are required to validate our outcomes.
format	article
author	Sajad Shahbazi Tara Zakerali
author_facet	Sajad Shahbazi Tara Zakerali
author_sort	Sajad Shahbazi
title	The inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer
title_short	The inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer
title_full	The inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer
title_fullStr	The inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer
title_full_unstemmed	The inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer
title_sort	inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an nf-kappa b silencer
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/441ce3bc39ca4b4c96c5bfeec3f4c704
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The inhibitory role of benzo-dioxole-piperamide on the phosphorylation process as an NF-Kappa B silencer

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