Molecular design based on receptor-independent pharmacophore: application to estrogen receptor ligands.
Estrogens, a group of steroid hormones, act primarily by regulating gene expression after binding with estrogen receptor (ER), a nuclear ligand-activated transcription factor, translocates to the nucleus after dimer formation, enhances the gene transcription. Estrogen Receptor Modulators (ERMs) have selective agonist and antagonist effects to different tissues, and the purpose of research on ERMs is to identify new potent and less toxic drug molecules. The present study has been focused on finding the structural requirements of ER ligand, using receptor-independent pharmacophore space modeling studies that can explore 3D structural features and configurations, responsible for the biological activity of structurally diverse compounds. The studies show (R=0.945, RMSD=2.186, Deltacost=677.354) the importance of hydrogen bond acceptors in the aromatic rings and a planner hydrophobic region in the molecular architecture along with critical geometrical distance between features are effectively crucial for binding with ER.
Islam
Md Ataul
MA
Department of Chemical Technology, University of Calcutta, Kolkata, India.
Nagar
Shuchi
S
Das
Suvadra
S
Mukherjee
Arup
A
Saha
Achintya
A
D015195:Drug Design; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D011960:Receptors, Estrogen / Q000737:chemistry / Q000187:drug effects*
D008024:Ligands; D011960:Receptors, Estrogen