Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment

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 pr...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-05, Vol.28 (11), p.4389
Main Authors: Méndez-Álvarez, Domingo, Torres-Rojas, Maria F, Lara-Ramirez, Edgar E, Marchat, Laurence A, Rivera, Gildardo
Format: Article
Language:English
Subjects:
Adipocytes
Body fat
Body mass index
Body weight loss
Cancer therapies
Drug screening
Drugs
estrogen receptor beta
Estrogen receptors
Estrogens
Gastrointestinal surgery
Hydrogen bonds
ligand-based virtual screening
Ligands
Molecular docking
Molecular dynamics
Obesity
Transcription factors
Weight control
Weight loss
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Summary: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 (-24.27 ± 0.34 kcal/mol), (-23.33 ± 0.3 kcal/mol), and (-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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28114389