دورية أكاديمية
Integrated molecular modeling and dynamics approaches revealed potential natural inhibitors of NF-κB transcription factor as breast cancer therapeutics.
| العنوان: | Integrated molecular modeling and dynamics approaches revealed potential natural inhibitors of NF-κB transcription factor as breast cancer therapeutics. |
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| المؤلفون: | Zubair M; Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan., Khalil S; Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan., Rasul I; Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan., Nadeem H; Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan., Noor F; Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan., Ahmad S; Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan., Alrumaihi F; Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia., Allemailem KS; Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia., Almatroudi A; Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia., Alshehri FF; College of Applied Medical Sciences, Shaqra University, Aldawadmi, Saudi Arabia., Alshehri ZS; College of Applied Medical Sciences, Shaqra University, Aldawadmi, Saudi Arabia. |
| المصدر: | Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023; Vol. 41 (24), pp. 14715-14729. Date of Electronic Publication: 2023 Jun 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: June 2012- : Oxon, UK : Taylor & Francis Original Publication: Guilderland, NY : Adenine Press, [c1983- |
| مواضيع طبية MeSH: | NF-kappa B*/metabolism , Breast Neoplasms*/drug therapy, Animals ; Humans ; Female ; NF-kappa B p52 Subunit/metabolism ; Molecular Docking Simulation ; NF-kappa B p50 Subunit/metabolism ; Mammals/metabolism |
| مستخلص: | Breast cancer is a silent killer malady among women and a serious economic burden in health care management. A case of breast cancer is diagnosed among women every 19 s, and every 74 s, a woman dies of breast cancer somewhere in the world. Despite the pop-up of progressive research, advanced treatment approaches, and preventive measures, breast cancer remains amplifying ailment. The nuclear factor kappa B (NF-κB) is a key transcription factor that links inflammation with cancer and is demonstrated as being involved in the tumorigenesis of breast cancer. The NF-κB transcription factor family in mammals consists of five proteins; c-Rel, RelA(p65), RelB, NF-κB1(p50), and NF-κB2(p52). The antitumor effect of NF-κB has also been explored in breast cancer, however, the actual treatment for breast cancer is yet to be discovered. This study is attributed to the identification of novel drug targets against breast cancer by targeting c-Rel, RelA(p65), RelB, NF-κB1(p50), and NF-κB2(p52) proteins. To identify the putative active compounds, a structure-based 3D pharmacophore model to the protein active site cavity was generated followed by virtual screening, molecular docking, and molecular dynamics (MD) simulation. Initially, a library of 45000 compounds were docked against the target protein and five compounds namely Z56811101, Z653426226, Z1097341967, Z92743432, and Z464101066 were selected for further analysis. The relative binding affinity of Z56811101, Z653426226, Z1097341967, Z92743432, and Z464101066 with NF-κB1 (p50), NF-κB2 (p52), RelA (p65), RelB, and c-Rel proteins were -6.8, -8, -7.0, -6.9, and -7.2 kcal/mol, respectively which remained stable throughout the simulations of 200 ns. Furthermore, all of these compounds depict maximum drug-like properties. Therefore, the proposed compounds can be a potential candidate for patients with breast cancer, but, experimental validation is needed to ensure their safety.Communicated by Ramaswamy H. Sarma. |
| فهرسة مساهمة: | Keywords: Breast cancer; NF-κB; molecular docking; molecular dynamic simulation; structure-based 3D pharmacophore model; virtual screening |
| المشرفين على المادة: | 0 (NF-kappa B) 0 (NF-kappa B p52 Subunit) 0 (NF-kappa B p50 Subunit) |
| تواريخ الأحداث: | Date Created: 20230610 Date Completed: 20231219 Latest Revision: 20231219 |
| رمز التحديث: | 20231219 |
| DOI: | 10.1080/07391102.2023.2214209 |
| PMID: | 37301608 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1538-0254 |
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| DOI: | 10.1080/07391102.2023.2214209 |