Ligand-Based and Structure-Based Virtual Screening of New Sodium Glucose Cotransporter Type 2 Inhibitors.
Diabetes mellitus
SGLT2
blood glucose
inhibitors
maximum common substructure
molecular docking
Journal
Medicinal chemistry (Shariqah (United Arab Emirates))
ISSN: 1875-6638
Titre abrégé: Med Chem
Pays: Netherlands
ID NLM: 101240303
Informations de publication
Date de publication:
2023
2023
Historique:
received:
01
05
2023
revised:
15
06
2023
accepted:
27
06
2023
pubmed:
3
8
2023
medline:
3
8
2023
entrez:
3
8
2023
Statut:
ppublish
Résumé
Diabetes mellitus is a metabolic disease that causes multiple complications and common comorbidities, which decreases the quality of life for people affected by the disease. Sodium glucose cotransporter type 2 (SGLT2) participates in the reabsorption of 90% of glucose in the kidneys; therefore, it is an attractive drug target for controlling blood glucose levels. The aim in this work was to obtain new potential SGLT2 inhibitors. A ligand-based virtual screening (LBVS) from the ZINC15, PubChem and ChemSpider databases using the maximum common substructure (MCS) scaffold was performed. A total of 341 compounds were obtained and analyzed by molecular docking on the active site of SGLT2. Subsequently, 15 compounds were selected for molecular dynamics (MD) simulation analysis. The compounds derived of spiroketal Sa1, Sa4, and Sa9 (≤ 3.5 Å) in complex with the receptor SGLT2 showed good stability during 120 ns of MD. These compounds are proposed as potential SGLT2 inhibitors.
Sections du résumé
BACKGROUND
BACKGROUND
Diabetes mellitus is a metabolic disease that causes multiple complications and common comorbidities, which decreases the quality of life for people affected by the disease. Sodium glucose cotransporter type 2 (SGLT2) participates in the reabsorption of 90% of glucose in the kidneys; therefore, it is an attractive drug target for controlling blood glucose levels.
OBJECTIVE
OBJECTIVE
The aim in this work was to obtain new potential SGLT2 inhibitors.
METHODS
METHODS
A ligand-based virtual screening (LBVS) from the ZINC15, PubChem and ChemSpider databases using the maximum common substructure (MCS) scaffold was performed.
RESULT
RESULTS
A total of 341 compounds were obtained and analyzed by molecular docking on the active site of SGLT2. Subsequently, 15 compounds were selected for molecular dynamics (MD) simulation analysis. The compounds derived of spiroketal Sa1, Sa4, and Sa9 (≤ 3.5 Å) in complex with the receptor SGLT2 showed good stability during 120 ns of MD.
CONCLUSION
CONCLUSIONS
These compounds are proposed as potential SGLT2 inhibitors.
Identifiants
pubmed: 37534786
pii: MC-EPUB-133362
doi: 10.2174/1573406419666230803122020
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1049-1060Informations de copyright
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