Computational explorations to gain insight into the structural features of TNF-α receptor I inhibitors

Sharifi, Mehdi; Alizadeh, Ali; Hamzeh‐Mivehroud, Maryam; Dastmalchi, Siavoush

doi:10.1007/s13738-018-1440-x

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…Generation of predictive models using 3D-QSAR approach for virtual screening has been widely used in drug design and discovery. 19 , 33 - 35 Here, it was intended to employ 3D-QSAR methodology to generate a model for the prediction of S1P 1 agonistic activity. To this end, the compounds with known activities towards S1P 1 ( Table 1 ) were docked into S1P 1 to obtain their receptor bound active conformations.…”

Section: Resultsmentioning

confidence: 99%

Drug Repurposing for Identification of S1P1 agonists with Potential Application in Multiple Sclerosis Using in Silico Drug Design Approaches

2022

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Purpose: Drug repurposing is an approach successfully used for discovery of new therapeutic applications for the existing drugs. The current study was aimed to use the combination of in silico methods to identify FDA-approved drugs with possible S1P1 agonistic activity useful in multiple sclerosis. Methods: For this, a 3D-QSAR model for the known 21 S1P1 agonists were generated based on 3D-QSAR approach and used to predict the possible S1P1 agonistic activity of FDA-approved drugs. Then, the selected compounds were screened by docking into S1P1 and S1P3 receptors to select the S1P1 potent and selective compounds. Further evaluation was carried out by molecular dynamics simulation studies where the S1P1 binding energies of selected compounds were calculated. Results: The analyses resulted in identification of cobicistat, benzonatate and brigatinib as the selective and potent S1P1 agonists with the binding energies of -85.93, -69.77 and -67.44 kcal.mol-1, calculated using MM-GBSA algorithm based on 50 ns molecular dynamics simulation trajectories. These valuesare which are better than that of siponimod (-59.35 kcal mol-1), a FDA approved S1P1 agonist indicated for MS treatment. Furthermore, similarity network analysis revealed that cobicistst and brigatinib are the most structurally favorable compounds to interact with S1P1. Conclusion: The findings in this study revealed that Cobicistat and Brigatinib can be evaluated in experimental studies as potential S1P1 agonist candidates useful in the treatment of multiple sclerosis.

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Section: Resultsmentioning

confidence: 99%

Drug Repurposing for Identification of S1P1 agonists with Potential Application in Multiple Sclerosis Using in Silico Drug Design Approaches

2022

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S1PR1 modulators in multiple sclerosis: Efficacy, safety, comparison, and chemical structure insights

Kandjani

Yaqoubi

Vahdati

et al. 2023

European Journal of Medicinal Chemistry

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Protective effects of astaxanthin on lipopolysaccharide-induced inflammation in bovine endometrial epithelial cells†

Wan

Zhang

Jin

et al. 2019

Biology of Reproduction

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Astaxanthin (AST), a natural antioxidant carotenoid, has been shown to exert anti-inflammatory effects. However, to our knowledge, no study has specifically addressed the potential protective effects of AST against bovine endometritis. The purpose of this study was to examine whether treatment with AST could protect endometrial epithelial cells against lipopolysaccharide (LPS)-induced inflammatory injury. Treatment of bovine endometrial (BEND) epithelial cell line with AST reduced LPS-induced production of interleukin-6 and tumor necrosis factor-alpha, increased the cellular activity of superoxide dismutase and catalase, decreased the proportion of apoptotic cells, and promoted the production of insulin-like growth factor and epithelial growth factor. The effects of AST were mediated through the downregulation of B-cell lymphoma 2 (Bcl-2) associated X, apoptosis regulator (Bax), and cleaved caspase-3 and through the upregulation of Bcl-2. Moreover, AST significantly increased the expression of the tight junction proteins (TJP) claudin, cadherin-1, and TJP1, which play an essential role in the maintenance of host endometrial defense barrier against pathogen infection. Collectively, these results demonstrated that treatment with AST protected against oxidative stress, prevented cell apoptosis, promoted BEND cells viability, and increased the production of growth factors, in addition to activating the endometrial defense barrier. Therefore, AST is a promising therapeutic agent for the prevention and treatment of endometritis. This finding is of utmost importance in the present times when the excessive use of antibiotics has resulted in the development of antibiotic-resistant bacteria.

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Computational explorations to gain insight into the structural features of TNF-α receptor I inhibitors

Cited by 3 publications

References 48 publications

Drug Repurposing for Identification of S1P1 agonists with Potential Application in Multiple Sclerosis Using in Silico Drug Design Approaches

Drug Repurposing for Identification of S1P1 agonists with Potential Application in Multiple Sclerosis Using in Silico Drug Design Approaches

S1PR1 modulators in multiple sclerosis: Efficacy, safety, comparison, and chemical structure insights

Protective effects of astaxanthin on lipopolysaccharide-induced inflammation in bovine endometrial epithelial cells†

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