Pharmacophore Mapping of Selective Estrogen Receptor Modulators

Breast cancer and osteoporosis are the common manifestations of post-menopausal women, and estrogen is responsible for these diseases. Selective Estrogen Receptor Modulators (SERMs) act as selective agonist and/or antagonistic effects to the different tissues, and use as first line treatment in estrogen responsive breast cancer and osteoporosis. To design promising SERM, the present study has been focused on receptor-independent pharmacophore mapping study that can explore 3D features and configurations responsible for biological activity of structurally diverse compounds. The study indicated that α-(Q=0.867, RMSD=1.433, ∆cost=183.609, Rts=0.511) and β-(Q=0.859, RMSD=1.173, ∆cost=110.862, Rts=0.526) subtypes are mapped with common hydrophobic and aromatic ring features, but the differences between subtypes are presence of one hydrogen bond (HB) donor and two hydrophobic regions in case of α-subtype, whereas β-subtype is additionally mapped with one HB acceptor and two aromatic rings features. The critical distances in 3D map of the features significantly differentiate the subtypes binding affinity. Key-Words: Estrogen receptor; SERMs; Pharmacophore mapping