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IL17
IL18
MD simulation
Molecular docking
chronic arthritis
polymer compounds
Journal
Journal of biomolecular structure & dynamics
ISSN: 1538-0254
Titre abrégé: J Biomol Struct Dyn
Pays: England
ID NLM: 8404176
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
medline:
12
6
2023
pubmed:
10
5
2022
entrez:
9
5
2022
Statut:
ppublish
Résumé
Two proinflammatory cytokines, IL17A and IL18, are observed to be elevated in the serum of gout patients and they play a crucial role in the development and worsening of inflammation, which has severe effects. In present study, we have combined molecular docking, molecular dynamics studies and MM-PBSA analysis to study the effectiveness of ethoxy phthalimide pyrazole derivatives (series 3a to 3e) as potential inhibitors against cytokines IL17A and IL18 as a druggable targets. The binding energy of the docked series ranges from -13.5 to -10.0 kcal/mol and extensively interacts with the amino acids in the active pocket of IL17A and IL18. Compound 3e had the lowest binding energy with IL17A at -12.6 kcal/mol compared to control allopurinol (3.32 kcal/mol). With IL18, compound 3a seems to have the lowest binding energy of -9.6 kcal/mol compared to control allopurinol (3.18 kcal/mol). In MD simulation studies, compound 3a forms a stable and energetically stabilized complex with the target protein. Depending on properties of the bound IL17A-3a and IL18-3a complexes was compared by means of MM-PBSA analysis. These derivatives can be used as a scaffold to develop promising IL17A and IL18 inhibitors to assess their potential for gouty arthritis and other related diseases. Communicated by Ramaswamy H. Sarma.
Identifiants
pubmed: 35532103
doi: 10.1080/07391102.2022.2071338
doi:
Substances chimiques
Interleukin-18
0
Interleukin-17
0
Allopurinol
63CZ7GJN5I
Antineoplastic Agents
0
Cytokines
0
phthalimide
1J6PQ7YI80
Phthalimides
0
Pyrazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM