Molecular mapping of heterocyclic diazene derivatives for estrogen receptor modulation.

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dc.contributor.authorIslam, Md Ataul
dc.contributor.authorMukherjee, Arup
dc.contributor.authorSaha, Achintya
dc.date.accessioned2012-08-10T08:07:52Z
dc.date.available2012-08-10T08:07:52Z
dc.date.issued2012-08
dc.description.abstractSelective 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.en_US
dc.identifier.citationIslam Md Ataul, Mukherjee Arup, Saha Achintya. Molecular mapping of heterocyclic diazene derivatives for estrogen receptor modulation. Indian Journal of Biochemistry & Biophysics. 2012 Aug; 49(4): 236-245.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/140241
dc.language.isoenen_US
dc.source.urihttps://nopr.niscair.res.in/handle/123456789/14539en_US
dc.subjectEstrogen receptoren_US
dc.subjectSERMsen_US
dc.subjectCoMFAen_US
dc.subjectCoMSIAen_US
dc.subjectPharmacophore mappingen_US
dc.subjectMolecular dockingen_US
dc.subject.meshHeterocyclic Compounds
dc.subject.meshHeterocyclic Compounds ---chemistry
dc.subject.meshHeterocyclic Compounds ---pharmacology
dc.subject.meshDNA-Binding Proteins
dc.subject.meshMolecular Docking Simulation --methods
dc.subject.meshModels, Molecular
dc.subject.meshReceptors, Estrogen --anlaysis
dc.subject.meshSelective Estrogen Receptor Modulators --analysis
dc.titleMolecular mapping of heterocyclic diazene derivatives for estrogen receptor modulation.en_US
dc.typeArticleen_US
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