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NISCAIR ONLINE PERIODICALS REPOSITORY (NOPR) >
NISCAIR PUBLICATIONS >
Research Journals >
Indian Journal of Biochemistry and Biophysics (IJBB) >
IJBB Vol.49 [2012] >
IJBB Vol.49(4) [August 2012] >
| Title: | Molecular mapping of heterocyclic diazene derivatives for estrogen receptor modulation |
| Authors: | Islam, Md Ataul
Mukherjee, Arup
Saha, Achintya |
| Keywords: | Estrogen receptor
SERMs
CoMFA
CoMSIA
Pharmacophore mapping
Molecular docking |
| Issue Date: | Aug-2012 |
| Publisher: | NISCAIR-CSIR, India |
| 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. |
| Page(s): | 236-245 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-0959 (Online); 0301-1208 (Print) |
| Source: | IJBB Vol.49(4) [August 2012]
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