## 2 Materials and Methods  
### Tools and Materials  
The hardware used for molecular docking comprised a personal laptop with an Intel(r) CoreTM i7-4600U processor, CPU @ 2.10 GHz 2.70 GHz, 8.00 GB of RAM, and a Windows 10 Pro version 22H2 64-bit operating system (Intel, Santa Clara, CA, USA). A computer with a Core Processor Intel(r) Xeon(r) CPU E5-2678 v3 @ 2.50 GHz, RAM 64 GB, a Graphic Card NVIDIA GeForce GTX 1070 Ti Core GPU, and a LINUX Ubuntu version 20.04 LTS operating system was used for molecular dynamics simulation. The software used is available free of charge for academic users the following: ChemDraw Professional 15.0 (PerkinElmer Informatics, Waltham, MA, USA) was used to draw the 2D structures of the ligand compounds, and Chem3D 15.0 (PerkinElmer Informatics, Waltham, MA, USA) was used to convert the 2D structure ligand into a 3D shape and optimize the energy. Autodock 4.2.6 and AutodockTools 1.5.6 (The Scripps Research Institute, San Diego, CA, USA), Command Prompt, and Notepad-11.2307.27.0 were used for ligand and receptor preparation and validation, as well as molecular docking simulations. BIOVIA Discovery Studio 2021 Client (Dassault Systemes, Waltham, MA, USA) was used for the preparation of receptors with native ligands to visualize the results of complex molecular docking, bonding between ligands and receptors, geometrical optimization, and overlays in the validation process. AMBER20 (Amber, San Francisco, CA, USA) was used to perform molecular dynamics (MD) simulations. VMD was used to visualize the protein-ligand complex and analyze the trajectory of the MD simulations. LigandScout 4.4.3 Advanced was used for pharmacophore modeling and screening. The web application used the following: SwissADME ([[http://www.swissadme.ch/](http://www.swissadme.ch/)]([http://www.swissadme.ch/](http://www.swissadme.ch/)), accessed on 15 December 2024) was used for the prediction of [PERSON]'s rule of five, CLC-Pred 2.0 ([[https://www.way2](https://www.way2)]([https://www.way2](https://www.way2)) drug.com/CLC-pred/, accessed on 20 December 2024) was used for the prediction of cell line cytotoxicity, PreADMET ([[https://preadmet.webservice.bmdrc.org/](https://preadmet.webservice.bmdrc.org/)]([https://preadmet.webservice.bmdrc.org/](https://preadmet.webservice.bmdrc.org/)), accessed on 25 December 2024) was used for the prediction of pharmacokinetic and toxicity profiles, and Protox-3.0 ([[https://tox.charite.de/protox3/](https://tox.charite.de/protox3/)]([https://tox.charite.de/protox3/](https://tox.charite.de/protox3/)), accessed on 10 January 2025) was used for the prediction of toxicity profiles. The materials used in this study included the 3D structure of the target receptor resulting from an X-ray crystallographic depiction of the human estrogen receptor alpha (hER\(\alpha\)) downloaded from the RCSB Protein Data Bank ([[https://www.rcsb.org/](https://www.rcsb.org/)]([https://www.rcsb.org/](https://www.rcsb.org/)), accessed on 20 January 2025) with PDB ID: 3 ERT. The ligand used as a reference drug was the structure of 4-OHT, raloxifene, and lasofoxifene. Further, the test ligands used were structures of the forty-five pyrazoline benzenesulfonamide derivatives.