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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
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

Pagination

4681-4695

Auteurs

Abhishek Kumar Verma (AK)

Department of Biosciences, Manipal University Jaipur, Dehmi Kalan, Off Jaipur-Ajmer Expressway, Jaipur, Rajasthan, India.

Md Shahadat Hossain (MS)

Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Sonapur, Noakhali, Bangladesh.

Sk Faisal Ahmed (SF)

Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Sonapur, Noakhali, Bangladesh.

Nasir Hussain (N)

Department of Chemistry, Faculty of Science and Technology, Mewar University, Chittorgarh, Rajasthan, India.

Mohammad Ashid (M)

Department of Chemistry, Faculty of Science and Technology, Mewar University, Chittorgarh, Rajasthan, India.

Sudhir K Upadhyay (SK)

Department of Environmental Science, V.B.S. Purvanchal University, Jaunpur, Uttar Pradesh, India.

Naveen Kumar Vishvakarma (NK)

Department of Biotechnology, Bilaspur, Chhattisgarh, India.

Ali Asger Bhojiya (AA)

Department of Science, U.S. Ostwal Science, Arts & Commerce College, Chittorgarh, India.

Sandeep Kumar Srivastava (SK)

Department of Biosciences, Manipal University Jaipur, Dehmi Kalan, Off Jaipur-Ajmer Expressway, Jaipur, Rajasthan, India.

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Classifications MeSH