Identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancer
Certain forms of breast cancer, particularly influenced by estrogen hormone, prompt the investigation of estrogen receptors as potential targets for therapeutic interventions. The drug discovery pipeline against breast cancer requires the identification and retention of crucial pharmacophoric featur...
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Elsevier
2025-06-01
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| Series: | Chemical Physics Impact |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S266702242500060X |
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| author | Rania A. Hussien Fatmah Ali S. Alasmary Vijay H. Masand Abdul Samad Rahul D. Jawarkar Gaurav S. Masand Sami A. Al-Hussain Magdi E.A. Zaki |
| author_facet | Rania A. Hussien Fatmah Ali S. Alasmary Vijay H. Masand Abdul Samad Rahul D. Jawarkar Gaurav S. Masand Sami A. Al-Hussain Magdi E.A. Zaki |
| author_sort | Rania A. Hussien |
| collection | DOAJ |
| description | Certain forms of breast cancer, particularly influenced by estrogen hormone, prompt the investigation of estrogen receptors as potential targets for therapeutic interventions. The drug discovery pipeline against breast cancer requires the identification and retention of crucial pharmacophoric features of inhibitors using a multitude of inhibitors comprising diverse scaffolds. In the present study, our focus was on conducting an e-QSAR (easy, efficient, economical, ecofriendly, and explainable QSAR), molecular docking and molecular dynamics simulations analyses on a diverse range of inhibitors that target Estrogen Receptor beta. The newly developed QSAR model upholds a balance between predictive accuracy with R2tr = 0.799, Q2LMO = 0.792, and CCCex = 0.886 and also provides mechanistic insights, thus adhering to the guidelines set forth by the Organisation for Economic Co-operation and Development (OECD). The analyses reveal that atoms with sp2-hybridization, specifically carbon and nitrogen atoms, have a significant impact on the binding profile along with lipophilic atoms. Additionally, a specific combination of hydrogen bond donors and acceptors involving carbon, nitrogen, and ring sulfur atoms also plays a crucial role. These novel findings have the potential to greatly aid future drug development targeting estrogen receptor beta. |
| format | Article |
| id | doaj-art-cb87e39b5f9441e0a4b349e960790c9f |
| institution | DOAJ |
| issn | 2667-0224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj-art-cb87e39b5f9441e0a4b349e960790c9f2025-08-20T03:20:05ZengElsevierChemical Physics Impact2667-02242025-06-011010087210.1016/j.chphi.2025.100872Identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancerRania A. Hussien0Fatmah Ali S. Alasmary1Vijay H. Masand2Abdul Samad3Rahul D. Jawarkar4Gaurav S. Masand5Sami A. Al-Hussain6Magdi E.A. Zaki7Department of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Kingdom of Saudi ArabiaSaudi food and drug authority, Riyadh, Saudi ArabiaDepartment of Chemistry, Vidya Bharati Mahavidyalaya, Amravati-444 602, Maharashtra, India; Corresponding authors.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tishk International University, Erbil 44001, IraqDepartment of Medicinal Chemistry, Dr. Rajendra Gode Institute of Pharmacy, University-Mardi Road, Amravati, Maharashtra, 444602, IndiaDepartment of Artificial Intelligence and Data Science, Dr. D. Y. Patil Institute of Technology, Sant Tukaram Nagar, Pimpri, Pune-411018, IndiaDepartment of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi ArabiaDepartment of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia; Corresponding authors.Certain forms of breast cancer, particularly influenced by estrogen hormone, prompt the investigation of estrogen receptors as potential targets for therapeutic interventions. The drug discovery pipeline against breast cancer requires the identification and retention of crucial pharmacophoric features of inhibitors using a multitude of inhibitors comprising diverse scaffolds. In the present study, our focus was on conducting an e-QSAR (easy, efficient, economical, ecofriendly, and explainable QSAR), molecular docking and molecular dynamics simulations analyses on a diverse range of inhibitors that target Estrogen Receptor beta. The newly developed QSAR model upholds a balance between predictive accuracy with R2tr = 0.799, Q2LMO = 0.792, and CCCex = 0.886 and also provides mechanistic insights, thus adhering to the guidelines set forth by the Organisation for Economic Co-operation and Development (OECD). The analyses reveal that atoms with sp2-hybridization, specifically carbon and nitrogen atoms, have a significant impact on the binding profile along with lipophilic atoms. Additionally, a specific combination of hydrogen bond donors and acceptors involving carbon, nitrogen, and ring sulfur atoms also plays a crucial role. These novel findings have the potential to greatly aid future drug development targeting estrogen receptor beta.http://www.sciencedirect.com/science/article/pii/S266702242500060XBrest cancerEstrogen receptor betaPharmacophore PatternQSAR |
| spellingShingle | Rania A. Hussien Fatmah Ali S. Alasmary Vijay H. Masand Abdul Samad Rahul D. Jawarkar Gaurav S. Masand Sami A. Al-Hussain Magdi E.A. Zaki Identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancer Chemical Physics Impact Brest cancer Estrogen receptor beta Pharmacophore Pattern QSAR |
| title | Identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancer |
| title_full | Identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancer |
| title_fullStr | Identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancer |
| title_full_unstemmed | Identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancer |
| title_short | Identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancer |
| title_sort | identification of pharmacophore synergism for optimization of estrogen receptor beta binders for hormone dependent forms of breast cancer |
| topic | Brest cancer Estrogen receptor beta Pharmacophore Pattern QSAR |
| url | http://www.sciencedirect.com/science/article/pii/S266702242500060X |
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