Benzofuran-based estrogen receptor α modulators as anti-cancer therapeutics: in silico and experimental studies.

In the search for new estrogen receptor alpha (ERα) modulators, a trial molecular screening was conducted and 5,6-dihydroxybenzofuran was identified as a possible drug target for ERα. The target molecular modelling molecule 1 and a series of 5,6-dihydroxybenzofurans have been synthesized and evaluated for their anti-proliferation activities against MCF-7 and MDA-MB-231 cells. From the SAR studies, potential functional groups have been identified, the two hydroxyl groups at C-5 and C-6 and the phenyl ring at C-2, which showed considerable cytotoxicity in MCF-7 breast cancer cells. In addition, the apoptotic abilities of the compounds have been measured in both MCF-7 ER(+) and MDA-MB-231 ER(-) breast cancer cells. The results demonstrated that our compounds inhibit MCF-7 breast cancer cells via ER(+). These preliminary results provide valuable information towards the identification of important functional groups present on 5,6-dihydroxybenzofuran, which could be a promising scaffold for designing novel ER ligands.

Phage display screening against a set of targets to establish peptide-based sugar mimetics and molecular docking to predict binding site.

A novel selection approach is presented to screen phage display peptide libraries against sets of receptors that share specificity for the same ligand. This strategy was applied to the discovery of glycomimetic peptides. Through these screens, a number of peptide clones were discovered that bind the lectins used in the screen, in a sugar competitive manner. In addition, the majority of the selected peptides demonstrate sugar type mimicry consistent with lectin specificity. Docking studies were conducted to establish whether the mimetic peptides bind to the lectin ConA at the sugar binding site or to a nearby, alternative site shown to bind to YPY-containing peptides previously discovered from single-target screens. Of the three cyclic peptides subjected to computational docking, CNTPLTSRC had the highest predicted affinity and CSRILTAAC demonstrated specificity for the sugar binding site comparable to the natural ligand itself.