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Lenchi, Nesrine, Maouche, Naima, Khemili-Talbi, Souad. (1404). Screening and docking molecular studies of natural products targeting overexpressed receptors HER-2 in breast cancer. سامانه مدیریت نشریات علمی, 80(3), 651-663. doi: 10.32592/ARI.2025.80.3.651
Nesrine Lenchi; Naima Maouche; Souad Khemili-Talbi. "Screening and docking molecular studies of natural products targeting overexpressed receptors HER-2 in breast cancer". سامانه مدیریت نشریات علمی, 80, 3, 1404, 651-663. doi: 10.32592/ARI.2025.80.3.651
Lenchi, Nesrine, Maouche, Naima, Khemili-Talbi, Souad. (1404). 'Screening and docking molecular studies of natural products targeting overexpressed receptors HER-2 in breast cancer', سامانه مدیریت نشریات علمی, 80(3), pp. 651-663. doi: 10.32592/ARI.2025.80.3.651
Lenchi, Nesrine, Maouche, Naima, Khemili-Talbi, Souad. Screening and docking molecular studies of natural products targeting overexpressed receptors HER-2 in breast cancer. سامانه مدیریت نشریات علمی, 1404; 80(3): 651-663. doi: 10.32592/ARI.2025.80.3.651

Screening and docking molecular studies of natural products targeting overexpressed receptors HER-2 in breast cancer

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مقاله 14، دوره 80، شماره 3، مرداد و شهریور 2025، صفحه 651-663    اصل مقاله (793.56 K)
نوع مقاله: Original Articles
شناسه دیجیتال (DOI): 10.32592/ARI.2025.80.3.651
نویسندگان
Nesrine Lenchi* 1؛ Naima Maouche2؛ Souad Khemili-Talbi3
1Department of Natural and Life Sciences, Faculty of Sciences, University Algiers 1 BenYoucef Benkhedda ,Algiers, Algeria
2Department of Natural and Life Sciences, Faculty of Sciences, University Algiers 1 BenYoucef Benkhedda, Algiers, Algeria
32Bioinformatics, Applied Microbiology and Biomolecules Laboratory, Faculty of Sciences, University of M'Hamed Bougara of Boumerdès. Algeria
چکیده
The first cancer to strike a community is breast cancer. Because of its extremely high mitotic activity, breast cancer that tests positive for HER 2 is thought to have a bad prognosis. Due to the effects caused by chemical drugs, patients are increasingly turning to natural medicine, such as phytotherapy and nutritherapy. The main objective of this study is to search, using a bioinformatics approach (molecular docking), for new non-toxic anti-cancer inhibitors by carrying out a screening of 102 ligands from natural and dietary compounds, likely to interact with the HER-2.The results of the virtual screening permit to choose 23 best compounds which can be proposed as the best inhibitors of HER-2. Lycopene would be a very promising ligand which presents a DeltaG of -9.82 kcal/mol, followed by Beta-carotene (DeltaG of -8.58), P-cumaric acid kcal/mol (DeltaG of -8.57) and Curcumin (DeltaG of -8.46). Another compounds; luteolin, anacardium (Anacardic acid) and alpha-Tocopherol were found to have the strongest inhibitory effects, with DeltaG values of -7.92 kcal/mol, -7.89 kcal/mol and-7.85 kcal/mol, respectively, and act directly on residues keys found in the hydrophobic pocket II (ATP binding site) and the hydrophobic region (the αC-β4 loop) of the EGFR domain. Pinoresino, Kaempferol and Caffeic acid with DeltaGs of -7.48 Kcal/mol, -6.88 Kcal/mol and -6.34 kcal/mol, and are three ligands specific to the conserved regions of the HER-2 receptor and interact with the tail respectively; C-terminal, the C-lobe activation loop and the N-lobe P loop of the tyrosine kinase domain. The comparison of Lapatinib (chemical compound) and quercetin (natural compound) have respectively DeltaG of -7.58 kcal/mol and -7.28 kcal/mol, form a hydrogen bond with the same residue of the hydrophobic region. All the natural molecules seem very promising and, after in vitro/in vivo tests, could constitute good substitutes for the chemotherapies currently used to treat breast cancers as well as other cancers.
کلیدواژه‌ها
Brest cancer؛ HER-2؛ Molecular docking؛ Natural compounds
مراجع
  1. Domeyer P-RJ, Sergentanis TN. New insights into the screening, prompt diagnosis, management, and prognosis of breast cancer. Journal of Oncology. 2020;2020:8597892.
  2. Dai X, Xiang L, Li T, Bai Z. Cancer hallmarks, biomarkers and breast cancer molecular subtypes. Journal of cancer. 2016;7(10):1281.
  3. Hsu JL, Hung M-C. The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer. Cancer and Metastasis Reviews. 2016;35:575-88.
  4. Maennling AE, Tur MK, Niebert M, Klockenbring T, Zeppernick F, Gattenlöhner S, et al. Molecular targeting therapy against EGFR family in breast cancer: progress and future potentials. Cancers. 2019;11(12):1826.
  5. Schlam I, Swain SM. HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now. NPJ breast cancer. 2021;7(1):56.
  6. Furrer D, Paquet C, Jacob S, Diorio C. The human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive biomarker: Molecular insights into HER2 activation and diagnostic implications. Cancer prognosis. 2018;5:11-21.
  7. Sharma D, Kumar S, Narasimhan B. Estrogen alpha receptor antagonists for the treatment of breast cancer: a review. Chemistry Central Journal. 2018;12:1-32.
  8. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic acids research. 2000;28(1):235-42.
  9. Aertgeerts K, Skene R, Yano J, Sang B-C, Zou H, Snell G, et al. Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. Journal of Biological Chemistry. 2011;286(21):18756-65.
  10. Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2023 update. Nucleic acids research. 2023;51(D1):D1373-D80.
  11. Irwin JJ, Sterling T, Mysinger MM, Bolstad ES, Coleman RG. ZINC: a free tool to discover chemistry for biology. Journal of chemical information and modeling. 2012;52(7):1757-68.
  12. Pires DE, Blundell TL, Ascher DB. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry. 2015;58(9):4066-72.
  13. Grosdidier A, Zoete V, Michielin O. SwissDock, a protein-small molecule docking web service based on EADock DSS. Nucleic acids research. 2011;39(suppl_2):W270-W7.
  14. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera—a visualization system for exploratory research and analysis. Journal of computational chemistry. 2004;25(13):1605-12.
  15. Yim-Im W, Sawatdichaikul O, Semsri S, Horata N, Mokmak W, Tongsima S, et al. Computational analyses of curcuminoid analogs against kinase domain of HER2. BMC bioinformatics. 2014;15:1-13.
  16. Aller P. Etude du domaine transmembranaire de recepteur tyrosine kinase dans un environnement membranaire. Aspects structuraux et mecanistiques explores par dynamique moleculaire: Université d'Orléans; 2004.
  17. Martin-Fernandez ML, Clarke DT, Roberts SK, Zanetti-Domingues LC, Gervasio FL. Structure and dynamics of the EGF receptor as revealed by experiments and simulations and its relevance to non-small cell lung cancer. Cells. 2019;8(4):316.
  18. Modi V, Dunbrack Jr RL. Defining a new nomenclature for the structures of active and inactive kinases. Proceedings of the National Academy of Sciences. 2019;116(14):6818-27.
  19. Vijayan R, He P, Modi V, Duong-Ly KC, Ma H, Peterson JR, et al. Conformational analysis of the DFG-out kinase motif and biochemical profiling of structurally validated type II inhibitors. Journal of medicinal chemistry. 2015;58(1):466-79.
  20. Klug LR, Kent JD, Heinrich MC. Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases. Pharmacology & therapeutics. 2018;191:123-34.
  21. Shih AJ, Telesco SE, Radhakrishnan R. Analysis of somatic mutations in cancer: molecular mechanisms of activation in the ErbB family of receptor tyrosine kinases. Cancers. 2011;3(1):1195-231.
  22. Ulrich L, Okines AF. Treating advanced unresectable or metastatic HER2-positive breast cancer: a spotlight on tucatinib. Breast Cancer: Targets and Therapy. 2021:361-81.
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