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Pharmacokinetic and Molecular Docking Analysis of Matricaria chamomilla Flavonoids Against Breast Cancer Targets

Yıl 2025, Cilt: 9 Sayı: 5, 54 - 61

Burcu Çöpcü

Öz

In this study, the pharmacokinetic, toxicological, and drug-likeness profiles of Quercetin, Luteolin, Apigenin natural flavonoids and active compounds found in the chamomile plant and Dibenzo-p-dioxin were comparatively analyzed using in silico methods. ADME (Absorption, Distribution, Metabolism, and Excretion) parameters, Lipinski’s Rule of Five, cellular permeability, blood-brain barrier penetration potential, metabolic stability, and cardiotoxicity risks were evaluated. The findings indicated that Apigenin possesses the most balanced pharmacokinetic profile, while Dibenzo-p-dioxin was found to be unsuitable for drug development due to its potential toxicity. Subsequently, molecular interactions of these flavonoids (Apigenin, Luteolin, Quercetin, and Dibenzo-p-dioxin) with proteins associated with breast cancer 1JNX (Estrogen Receptor α) and 6CZ2 (HER2 receptor) were investigated using molecular docking analysis. Accordingly, the aim of this study is to evaluate the pharmaceutical potential of the selected compounds using computational methods, compare their strengths and weaknesses, and identify which compounds are more suitable as clinical drug candidates.

Anahtar Kelimeler

Apigenin Luteolin Quercetin Dibenzo-p-dioxin Molecular Docking ADME Breast Cancer

Kaynakça

  • [1] Kumar, S., Pandey, A. K. Chemistry and biological activities of flavonoids: an overview. The scientific world journal, (1) (2013) 162750.
  • [2] Tang, D., Chen, K., Huang, L., Li, J. Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert opinion on drug metabolism & toxicology, 13 (3) (2017) 323-330.
  • [3] Manach, C., Williamson, G., Morand, C., Scalbert, A., Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American journal of clinical nutrition, 81 (1) (2005) 230S-242S.
  • [4] Walle, T. Bioavailability of flavonoids. Free Radical Biology and Medicine, 38 (2) (2007) 156–158.
  • [5] Pires, D. E., Blundell, T. L., Ascher, D. B. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry, 58 (9) (2015) 4066-4072.
  • [6] Schecter, A., Birnbaum, L., Ryan, J. J., Constable, J. D. Dioxins: an overview. Environmental research, 101 (3) (2006) 419-428.
  • [7] Panche, A. N., Diwan, A. D., Chandra, S. R. Flavonoids: an overview. Journal of nutritional science, 5, (2016) e47.
  • [8] Middleton, Jr. E., Kandaswami, C., Theoharides, T. C. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacological Reviews, 52 (4) (2000) 673–751.
  • [9] Shukla, S., Gupta, S. Apigenin: a promising molecule for cancer prevention. Pharmaceutical research, 27 (2010). 962-978.
  • [10] Lin, Y., Shi, R., Wang, X., Shen, H. M. Luteolin, a flavonoid with potential for cancer prevention and therapy. Current cancer drug targets, 8 (7) (2008) 634-646.
  • [11] Yang, F., Song, L., Wang, H., Wang, J., Xu, Z., Xing, N. Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential. Oncology reports, 33 (6) (2015) 2659-2668.
  • [12] Khan, M. F., Alam, M. M., Verma, G., Akhtar, W., Rizvi, M. A., Ali, A., Shaquiquzzaman, M. Molecular interactions of dioxins and DLCs with the ketosteroid receptors: an in silico risk assessment approach. Toxicology Mechanisms and Methods, 27 (2) (2017). 151-163.
  • [13] Bray, F. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68 (6) (2018) 394–424.
  • [14] Waks, A. G., Winer, E. P. Breast cancer treatment: a review. Jama, 321 (3) (2019) 288-300.
  • [15] Brzozowski, A. M., Pike, A. C., Dauter, Z., Hubbard, R. E., Bonn, T., Engström, O., Carlquist, M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature, 389 (6652) (1997) 753-758.
  • [16] Burgess, A. W., Cho, H. S., Eigenbrot, C., Ferguson, K. M., Garrett, T. P., Leahy, D. J., Yokoyama, S. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Molecular cell, 12 (3) (2003) 541-552.
  • [17] Clarke, R., Tyson, J. J., Dixon, J. M. Endocrine resistance in breast cancer–an overview and update. Molecular and cellular endocrinology, 418 (2015) 220-234.
  • [18] Nahta, R., Esteva, F. J. HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Research, 9 (6) (2007) 213.
  • [19] Schrödinger, LLC. QikProp, version 6.1. New York, NY: Schrödinger, LLC. (2023).
  • [20] Lipinski, C. A., Lombardo, F., Dominy, B. W., Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 46 (1–3) (2001) 3–26.
  • [21] Cavalli, A., Poluzzi, E., De Ponti, F., Recanatini, M. Toward a pharmacophore for drugs inducing the long QT syndrome: Insights from a CoMFA study of HERG K⁺ channel blockers. Journal of Medicinal Chemistry, 45 (18) (2002) 3844–3853.
  • [22] Wang, W., Sun, C., Mao, L., Ma, P., Liu, F., Yang, J., & Gao, Y. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends in food science & technology, 56 (2016) 21-38.
  • [23] Lerch, S., Siegenthaler, R., Numata, J., Moenning, J. L., Dohme-Meier, F., & Zennegg, M. Accumulation Rate, Depuration Kinetics, and Tissue Distribution of Polychlorinated Dibenzo-p-Dioxins and Dibenzofurans (PCDD/Fs) in Suckler Ewes (Ovis aries). Journal of Agricultural and Food Chemistry, 72 (26) (2024) 14941-14955.
  • [24] United States Environmental Protection Agency. (2025). Learn about dioxin.
  • [25] Mocarelli, P., Gerthoux, P. M., Patterson Jr, D. G., Milani, S., Limonta, G., Bertona, M., Needham, L. L. Dioxin exposure, from infancy through puberty, produces endocrine disruption and affects human semen quality. Environmental health perspectives, 116 (1) (2008) 70-77.

Yıl 2025, Cilt: 9 Sayı: 5, 54 - 61

Burcu Çöpcü

Öz

Kaynakça

  • [1] Kumar, S., Pandey, A. K. Chemistry and biological activities of flavonoids: an overview. The scientific world journal, (1) (2013) 162750.
  • [2] Tang, D., Chen, K., Huang, L., Li, J. Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert opinion on drug metabolism & toxicology, 13 (3) (2017) 323-330.
  • [3] Manach, C., Williamson, G., Morand, C., Scalbert, A., Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American journal of clinical nutrition, 81 (1) (2005) 230S-242S.
  • [4] Walle, T. Bioavailability of flavonoids. Free Radical Biology and Medicine, 38 (2) (2007) 156–158.
  • [5] Pires, D. E., Blundell, T. L., Ascher, D. B. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry, 58 (9) (2015) 4066-4072.
  • [6] Schecter, A., Birnbaum, L., Ryan, J. J., Constable, J. D. Dioxins: an overview. Environmental research, 101 (3) (2006) 419-428.
  • [7] Panche, A. N., Diwan, A. D., Chandra, S. R. Flavonoids: an overview. Journal of nutritional science, 5, (2016) e47.
  • [8] Middleton, Jr. E., Kandaswami, C., Theoharides, T. C. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacological Reviews, 52 (4) (2000) 673–751.
  • [9] Shukla, S., Gupta, S. Apigenin: a promising molecule for cancer prevention. Pharmaceutical research, 27 (2010). 962-978.
  • [10] Lin, Y., Shi, R., Wang, X., Shen, H. M. Luteolin, a flavonoid with potential for cancer prevention and therapy. Current cancer drug targets, 8 (7) (2008) 634-646.
  • [11] Yang, F., Song, L., Wang, H., Wang, J., Xu, Z., Xing, N. Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential. Oncology reports, 33 (6) (2015) 2659-2668.
  • [12] Khan, M. F., Alam, M. M., Verma, G., Akhtar, W., Rizvi, M. A., Ali, A., Shaquiquzzaman, M. Molecular interactions of dioxins and DLCs with the ketosteroid receptors: an in silico risk assessment approach. Toxicology Mechanisms and Methods, 27 (2) (2017). 151-163.
  • [13] Bray, F. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68 (6) (2018) 394–424.
  • [14] Waks, A. G., Winer, E. P. Breast cancer treatment: a review. Jama, 321 (3) (2019) 288-300.
  • [15] Brzozowski, A. M., Pike, A. C., Dauter, Z., Hubbard, R. E., Bonn, T., Engström, O., Carlquist, M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature, 389 (6652) (1997) 753-758.
  • [16] Burgess, A. W., Cho, H. S., Eigenbrot, C., Ferguson, K. M., Garrett, T. P., Leahy, D. J., Yokoyama, S. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Molecular cell, 12 (3) (2003) 541-552.
  • [17] Clarke, R., Tyson, J. J., Dixon, J. M. Endocrine resistance in breast cancer–an overview and update. Molecular and cellular endocrinology, 418 (2015) 220-234.
  • [18] Nahta, R., Esteva, F. J. HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Research, 9 (6) (2007) 213.
  • [19] Schrödinger, LLC. QikProp, version 6.1. New York, NY: Schrödinger, LLC. (2023).
  • [20] Lipinski, C. A., Lombardo, F., Dominy, B. W., Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 46 (1–3) (2001) 3–26.
  • [21] Cavalli, A., Poluzzi, E., De Ponti, F., Recanatini, M. Toward a pharmacophore for drugs inducing the long QT syndrome: Insights from a CoMFA study of HERG K⁺ channel blockers. Journal of Medicinal Chemistry, 45 (18) (2002) 3844–3853.
  • [22] Wang, W., Sun, C., Mao, L., Ma, P., Liu, F., Yang, J., & Gao, Y. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends in food science & technology, 56 (2016) 21-38.
  • [23] Lerch, S., Siegenthaler, R., Numata, J., Moenning, J. L., Dohme-Meier, F., & Zennegg, M. Accumulation Rate, Depuration Kinetics, and Tissue Distribution of Polychlorinated Dibenzo-p-Dioxins and Dibenzofurans (PCDD/Fs) in Suckler Ewes (Ovis aries). Journal of Agricultural and Food Chemistry, 72 (26) (2024) 14941-14955.
  • [24] United States Environmental Protection Agency. (2025). Learn about dioxin.
  • [25] Mocarelli, P., Gerthoux, P. M., Patterson Jr, D. G., Milani, S., Limonta, G., Bertona, M., Needham, L. L. Dioxin exposure, from infancy through puberty, produces endocrine disruption and affects human semen quality. Environmental health perspectives, 116 (1) (2008) 70-77.
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Moleküler Görüntüleme
Bölüm Research Article
Yazarlar

Burcu Çöpcü 0000-0001-9372-1867

Erken Görünüm Tarihi 23 Haziran 2025
Yayımlanma Tarihi
Gönderilme Tarihi 12 Haziran 2025
Kabul Tarihi 20 Haziran 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 9 Sayı: 5

Kaynak Göster

APA Çöpcü, B. (2025). Pharmacokinetic and Molecular Docking Analysis of Matricaria chamomilla Flavonoids Against Breast Cancer Targets. Turkish Computational and Theoretical Chemistry, 9(5), 54-61.
AMA Çöpcü B. Pharmacokinetic and Molecular Docking Analysis of Matricaria chamomilla Flavonoids Against Breast Cancer Targets. Turkish Comp Theo Chem (TC&TC). Haziran 2025;9(5):54-61.
Chicago Çöpcü, Burcu. “Pharmacokinetic and Molecular Docking Analysis of Matricaria Chamomilla Flavonoids Against Breast Cancer Targets”. Turkish Computational and Theoretical Chemistry 9, sy. 5 (Haziran 2025): 54-61.
EndNote Çöpcü B (01 Haziran 2025) Pharmacokinetic and Molecular Docking Analysis of Matricaria chamomilla Flavonoids Against Breast Cancer Targets. Turkish Computational and Theoretical Chemistry 9 5 54–61.
IEEE B. Çöpcü, “Pharmacokinetic and Molecular Docking Analysis of Matricaria chamomilla Flavonoids Against Breast Cancer Targets”, Turkish Comp Theo Chem (TC&TC), c. 9, sy. 5, ss. 54–61, 2025.
ISNAD Çöpcü, Burcu. “Pharmacokinetic and Molecular Docking Analysis of Matricaria Chamomilla Flavonoids Against Breast Cancer Targets”. Turkish Computational and Theoretical Chemistry 9/5 (Haziran 2025), 54-61.
JAMA Çöpcü B. Pharmacokinetic and Molecular Docking Analysis of Matricaria chamomilla Flavonoids Against Breast Cancer Targets. Turkish Comp Theo Chem (TC&TC). 2025;9:54–61.
MLA Çöpcü, Burcu. “Pharmacokinetic and Molecular Docking Analysis of Matricaria Chamomilla Flavonoids Against Breast Cancer Targets”. Turkish Computational and Theoretical Chemistry, c. 9, sy. 5, 2025, ss. 54-61.
Vancouver Çöpcü B. Pharmacokinetic and Molecular Docking Analysis of Matricaria chamomilla Flavonoids Against Breast Cancer Targets. Turkish Comp Theo Chem (TC&TC). 2025;9(5):54-61.

Journal Full Title: Turkish Computational and Theoretical Chemistry


Journal Abbreviated Title: Turkish Comp Theo Chem (TC&TC)