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- Title
Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment.
- Authors
Méndez-Álvarez, Domingo; Torres-Rojas, Maria F.; Lara-Ramirez, Edgar E.; Marchat, Laurence A.; Rivera, Gildardo
- Abstract
Obesity is a pandemic and a serious health problem in developed and undeveloped countries. Activation of estrogen receptor beta (ERβ) has been shown to promote weight loss without modifying caloric intake, making it an attractive target for developing new drugs against obesity. This work aimed to predict new small molecules as potential ERβ activators. A ligand-based virtual screening of the ZINC15, PubChem, and Molport databases by substructure and similarity was carried out using the three-dimensional organization of known ligands as a reference. A molecular docking screening of FDA-approved drugs was also conducted as a repositioning strategy. Finally, selected compounds were evaluated by molecular dynamic simulations. Compounds 1 (−24.27 ± 0.34 kcal/mol), 2 (−23.33 ± 0.3 kcal/mol), and 6 (−29.55 ± 0.51 kcal/mol) showed the best stability on the active site in complex with ERβ with an RMSD < 3.3 Å. RMSF analysis showed that these compounds do not affect the fluctuation of the Cα of ERβ nor the compactness according to the radius of gyration. Finally, an in silico evaluation of ADMET showed they are safe molecules. These results suggest that new ERβ ligands could be promising molecules for obesity control.
- Subjects
UNITED States. Food &; Drug Administration; MOLECULAR docking; ESTROGEN receptors; DYNAMIC simulation; DRUG therapy; WEIGHT loss; SMALL molecules; MOLECULAR dynamics
- Publication
Molecules, 2023, Vol 28, Issue 11, p4389
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules28114389