Structure-based design of eugenol analogs as potential estrogen receptor antagonists

Abstract

Eugenol is an essential oil mainly found in the buds and leaves of clove (Syzygium aromaticum (L.) Merrill and Perry), which has been reported to have activity on inhibition of cell proliferation and apoptosis induction in human MCF-7 breast cancer cells. This biological activity is correlated to its activity as an estrogen receptor antagonist. In this article, we present the construction and validation of structure-based virtual screening (SBVS) protocols to identify the potent estrogen receptor α (ER) antagonists. The selected protocol, which gave acceptable enrichment factors as a virtual screening protocol, subsequently used to virtually screen eugenol, its analogs and their dimers. Based on the virtual screening results, dimer eugenol of 4-[4-hydroxy-3-(prop-2-en-1- yl)phenyl]-2-(prop-2-en-1-yl)phenol is recommended to be developed further in order to discover novel and potent ER antagonists.

Binary Quantitative Structure-Activity Relationship Analysis in Retrospective Structure-Based Virtual Screening Campaigns Targeting Estrogen Receptor Alpha

“…All compounds identified as "bad" by SPORES1.3 in this step were removed and tagged as in actives or negatives (N). Virtual target (protein.mol2 and water.mol2) and docking configuration file (plants.config) were obtained from Anita et al [30]. Each compound was docked independently using PLANTS1.2 [21] five times, followed by PLIF identification using PyPLIF [7,8].…”

“…and GLY420 were identified as pivotal molecular determinants in ERα-ligand binding by both SBVS_2 and SBVS_3. The hydrogen bond network involving ARG394 as donors has identified in the crystal structure 3ERT [38] employed in the first SBVS to identify potent ERα ligand using PLANTS docking software [30]. Since the side chain of GLY420 could not serve as hydrogen bond acceptor, the O carbonyl in the main chain is the one that serves as the acceptor.…”

Computer-Aided Drug Repurposing: A Cyclooxygenase-2 Inhibitor Celecoxib as a Ligand for Estrogen Receptor Alpha

“…The ZINC code of celecoxib was ZINC02570895 [14,22]. Configuration files to perform in silico tests to identify celecoxib as ERα ligand by using PLANTS docking software were obtained from Anita et al [17] [23]. This research used US BIO ERα primary antibody [23].…”

“…The previously published procedure by Anita et al [17] was employed to dock celecoxib to ERα binding pocket three times [17,20]. The docked poses resulted in the molecular docking simulations were subsequently subjected to PyPLIF to identify their PLIF [19].…”

“…The research aimed to employ computer-aided drug repurposing strategy [16] to verify the activity of celecoxib as a potent ligand for ERα. The SBVS protocol used to perform in silico tests was initially constructed and retrospectively validated by Anita et al [17] to identify ERα antagonists [18]. By incorporating PyPLIF [19], subsequently the protocol was re-validated and and reported that the protocol employing PyPLIF has a significantly better quality [19][20][21].…”