Background: Curcumin and its derivatives have shown their activity against anticancer. Asymmetric Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) is a development compound of Asymmetric Monocarbonyl Analogs of Curcumin (AMACs) that have demonstrated cytotoxic inhibitory activity against breast cancer. The alpha estrogen receptor (RE-α) plays a role in breast development and signal pro-proliferation activation in the normal breast and breast that has cancer. This study aims to find potential AIACs compounds as breast anticancer screening of 186 AIACs design compounds based on ligand-based, and structure-based.

Methods: The method used in screening 186 designs of AIACs compounds was based on ligand-based based on the pharmacophore model, and molecular docking with  AutoDockTools (v 4.2) integrated LigandScout software 4.09.1.

Results: The model 1 of the pharmacophore model was chosen to screen from 186 compounds to 14 compounds. In model 1 there were three types of chemical features including hydrophobic interactions, hydrogen bond acceptor interactions, and aromatic, and model 1 was the model with the best value hit a score of 0.7718. Fourteen selected compounds followed by molecular docking obtained free energy values ​​of ΔG in the ten best compounds , namely compounds: 6A6, 6B1, 6B2, 6B3, 6B4 6B7, 6B8, 6B9, 6B10, and 6B11. The hydrophobic interaction patterns of 5 compounds, namely 6B7, 6B8, 6B9, 6B10, and 6B11, have similar triangular patterns and two difference in distance that are not much different.

Conclusion: Finally, ten hit compounds were considered as novel potential estrogen receptor α inhibitors.