Estrogen Receptor Alpha Binders for Hormone-Dependent Forms of Breast Cancer: e-QSAR and Molecular Docking Supported by X-ray Resolved Structures

  • ACS Omega. 2024 Mar 29;9(14):16759-16774. doi: 10.1021/acsomega.4c00906.
Vijay H Masand  1 ,  Sami A Al-Hussain  2 ,  Abdullah Y Alzahrani  3 ,  Aamal A Al-Mutairi  2 ,  Rania A Hussien  4 ,  Abdul Samad  5 ,  Magdi E A Zaki  2
Affiliations
  • 1. Department of Chemistry, Vidya Bharati Mahavidyalaya, Amravati 444 602, Maharashtra, India.
  • 2. Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi Arabia.
  • 3. Department of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail 61421, Saudi Arabia.
  • 4. Department of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Kingdom of Saudi Arabia.
  • 5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tishk International University, Erbil 44001, Iraq.
PMID: 38617692 DOI: 10.1021/acsomega.4c00906
Abstract

Cancer, a life-disturbing and lethal disease with a high global impact, causes significant economic, social, and health challenges. Breast Cancer refers to the abnormal growth of cells originating from breast tissues. Hormone-dependent forms of breast Cancer, such as those influenced by estrogen, prompt the exploration of estrogen receptors as targets for potential therapeutic interventions. In this study, we conducted e-QSAR molecular docking and molecular dynamics analyses on a diverse set of inhibitors targeting Estrogen receptor alpha (ER-α). The e-QSAR model is based on a genetic algorithm combined with multilinear regression analysis. The newly developed model possesses a balance between predictive accuracy and mechanistic insights adhering to the OECD guidelines. The e-QSAR model pointed out that sp2-hybridized carbon and nitrogen atoms are important atoms governing binding profiles. In addition, a specific combination of H-bond donors and acceptors with carbon, nitrogen, and ring sulfur atoms also plays a crucial role. The results are supported by molecular docking, MD simulations, and X-ray-resolved structures. The novel results could be useful for future drug development for ER-α.

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