Department of Chemistry, University of Puerto Rico at Mayagüez, Puerto Rico - Abstract
While early detection technology for cancer has been peruse as one of the priorities to extend life expectancy, small molecule therapeutic drugs treatment remains as the first line of defend again cancer problems. The hormone dependency for Estrogen Receptor positive breast cancer has led to the development of therapeutic drugs known as selective estrogen receptor modulators. However, selective estrogen receptor modulators drugs have been limited to only few candidates were tamoxifen is considered the golden standard. Despite the short-term success of tamoxifen application, long-term treatment of this drug has been associated with: breast cancer resistance in hormone therapy and an increased incidence of endometrial cancer by 4to 6.9-fold. New advances in the characterization, at atomic level, of protein-ligand complexes and the development of new algorithms and computational chemistry, the rational development of more selective and active drugs has been possible in medicinal chemistry. In this context, an in silico virtual screening on the Estrogen Receptor-Ligand Binding Domain has performed in order to identify new lead candidates as templates for new drugs in this study. A library of commercial available compounds (~650,000 drug-like small molecules) were docked into the Estrogen Receptor-Ligand Binding Domain using as template the protein-ligand complex crystal structure with 4-hydroxytamoxifen. Particularly attention has been made to the principal structural components of the best docking results for the library compounds entering the protein ligand binding domain and lateral side chain toward the alphahelix 12 of the Estrogen Receptor alpha that could result in the stabilization of protein antagonist form.