Molecular mapping of heterocyclic diazene derivatives for estrogen receptor modulation.
Indian J Biochem Biophys
;
2012 Aug; 49(4): 236-245
Article
in English
| IMSEAR
| ID: sea-140241
ABSTRACT
Selective estrogen receptor modulators (SERMs) are effectively used in hormone replacement therapy (HRT) by reducing post-menopausal symptoms, including hormone-responsive breast cancer and osteoporosis. The present study explored the pharmacophore features of diazene derivatives for selective estrogen receptor (ER) modulation using quantitative structure activity relationship (QSAR) and space modeling approaches. The 2D-QSAR models (R2α = 0.907, Q2α = 0.700, R2pred-α = 0.735; R2β = 0.913, Q2β = 0.756, R2pred-β = 0.745) showed the importance of orbital energies, hydrophobicity, refractivity and atomic charges for selective binding affinity to ER. In 3D-QSAR, molecular field (CoMFA, R2α = 0.948, Q2 = 0.720, R2pred-α = 0.708; R2β = 0.994, Q2β = 0.541, R2pred-β = 0.721) and similarity models (CoMSIA, R2α = 0.984, Q2α = 0.793, R2pred-α = 0.738; R2β = 0.996, Q2β = 0.681, R2pred-β = 0.725) indicated that steric and hydrophobic properties were important for binding selectivity. Space modeling study (R2α = 0.885, Q2α = 0.855, R2pred-α = 0.666; R2β = 0.872, Q2β = 0.883, R2pred-β = 0.814) revealed that hydrophobic and aromatic ring features were important for both subtypes, whereas hydrogen bond (HB) acceptor and donor were crucial for β- and α-subtypes, respectively. Interactions observed between ligand and catalytic residues at the active site in docking study substantiated the developed model which may be successfully used in high throughput screening (HTS) to obtain promising lead molecules for selective estrogen therapy.
Full text:
Available
Index:
IMSEAR (South-East Asia)
Main subject:
Models, Molecular
/
Receptors, Estrogen
/
Selective Estrogen Receptor Modulators
/
DNA-Binding Proteins
/
Molecular Docking Simulation
/
Heterocyclic Compounds
Language:
English
Journal:
Indian J Biochem Biophys
Year:
2012
Type:
Article
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