Structure-based drug design-guided identification of estrogen receptor binders.
Mol Divers
; 2023 Jun 08.
Article
in En
| MEDLINE
| ID: mdl-37289383
ABSTRACT
Cancer is one of the life-threatening diseases and the second leading cause of death in the world. The estrogen receptor can be considered as one of the significant drug targets for cancer. A large number of clinically used anticancer drugs were identified from phytochemicals. Multiple literatures suggested that extracts of Datura sp. significantly inhibit estrogen receptors associated with human cancer. In the present study, all reported natural products present in Datura sp. were subjected to molecular docking against estrogen receptors. The top hits were shortlisted based on binding orientation and docking score and subjected to molecular dynamics simulation to explore the conformational stability followed by binding energy calculation. The ligand [(1S,5R)-8-Methyl-8-Azabicyclo [3.2.1] Octan-3-yl] (2R)-3-Hydroxy-2-Phenylpropanoate depicts highly acceptable MD simulations outcomes and drug-likeness profile. Knowledge-based de novo design and similar ligand screening were executed using the structural information. The designed ligand DL-50 exhibited satisfactory binding, drug-likeness profile, and well-accepted ADMET profile followed by easy synthetic accessibility which further requires experimental validation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Diagnostic_studies
/
Prognostic_studies
Language:
En
Journal:
Mol Divers
Journal subject:
BIOLOGIA MOLECULAR
Year:
2023
Document type:
Article
Affiliation country:
India