Araştırma Makalesi
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ELTROMBOPAG VE İNSAN SERUM ALBÜMİNİ ARASINDAKİ ETKİLEŞİM: FLORESANS VE ELEKTROKİMYASAL ÇALIŞMALAR

Yıl 2025, Cilt: 49 Sayı: 3, 21 - 21

Merve Yence , Ahmet Çetinkaya , Esen Bellur Atici , Sibel A. Özkan

https://doi.org/10.33483/jfpau.1663961

Öz

Amaç: Bu araştırmada Eltrombopag (EB) ile İnsan Serum Albümini (HSA) arasındaki etkileşim floresan spektroskopisi ve voltametri ile incelenerek sönümlenme mekanizması açıklanmıştır.
Gereç ve Yöntem: Elektrokimyasal çalışmalar, pH 4'te asetat tampon çözeltisinde (AB) diferansiyel darbe voltametrisi (DPV) ile gerçekleştirildi. Floresan çalışmaları için EB, HSA ve EB ve HSA çözeltilerinin karışımı, %20 DMSO içeren pH 4.7 AB ile tasarlandı.
Sonuç ve Tartışma: EB ve HSA arasındaki etkileşim floresan ve elektrokimyasal titrasyonlar ile incelendi ve sönümlenme etkisi ile pik kayması elde edildi. Floresan titrasyonları, EB'nin HSA sönümleme işleminin statik olduğunu ve hipsokromik bir kayma olduğunu gösterir. Termodinamik parametrelerin ve daha yüksek bağlanma sabitlerinin analizi güçlü ve kendiliğinden bir etkileşimin olduğunu ortaya koydu. Elektrokimyasal titrasyonlar, EB'nin HSA'ya interkalasyonunu gösterir.

Anahtar Kelimeler

Diferansiyel darbe voltametrisi eltrombopag floresan spektroskopisi ilaç protein etkileşimi insan serum albümini

Kaynakça

  • 1. Ahmed, S., Bashir, Q., Bassett, R., Poon, M.Y.C., Valdez, B., Konoplev, S., Alousi, A.M., Andersson, B. S., Ciurea, S., Hosing, C., Jones, R., Kebriaei, P., Khouri, I., Kim, S., Nieto, Y., Olson, A., Oran, B., Parmar, S., Qazilbash, M. H., Popat, U. (2021). Eltrombopag for post-transplantation thrombocytopenia: Results of phase II randomized, double-blind, placebo-controlled trial. Transplantation and Cellular Therapy, 27(5), 430.e1-430.e7. [CrossRef]
  • 2. Samarkandi, H., Al Nahedh, M., Alfattani, A., Alsharif, F., Bakshi, N., Rasheed, W., Alfraih, F., Alhumaid, M., Alkhudair, N., Alhayli, S., Alsaedi, H., Shaheen, M., Hanbali, A., Hashmi, S.K., Devol, E., Alseraihy, A., Alzahrani, H., Aljurf, M. (2020). Evaluation of eltrombopag in thrombocytopenia post Hematopoietic cell transplantation: Rertrospective observational trial. Hematology/Oncology and Stem Cell Therapy. [CrossRef]
  • 3. Su, M.Y., Chang, H.H., Chou, S.W., Lu, M.Y., Yang, Y.L., Lin, D.T., Lin, K.H., Jou, S.T. (2021). Role of eltrombopag in severe aplastic anemia treatment in children. Pediatrics & Neonatology, 62(6), 655-657. [CrossRef]
  • 4. Weingarten, S.J., Friedman, D., Arora, A. (2021). Eltrombopag use for refractory immune thrombocytopenia in pregnancy: A case report. Case Reports in Women’s Health, 29, e00281. [CrossRef]
  • 5. Winer, E.S., Safran, H., Karaszewska, B., Bauer, S., Khan, D., Doerfel, S., Burgess, P., Kalambakas, S., Mostafa Kamel, Y., Forget, F. (2017). Eltrombopag for thrombocytopenia in patients with advanced solid tumors receiving gemcitabine-based chemotherapy: A randomized, placebo-controlled phase 2 study. International Journal of Hematology, 106(6), 765-776. [CrossRef]
  • 6. Menezes, T.M., Neto, A.M. da S., Gubert, P., Neves, J.L. (2021). Effects of human serum albumin glycation on the interaction with the tyrosine kinase inhibitor pazopanib unveiled by multi-spectroscopic and bioinformatic tools. Journal of Molecular Liquids, 340, 116843. [CrossRef]
  • 7. Tao, H., Wang, R., Sheng, W., Zhen, Y. (2021). The development of human serum albumin-based drugs and relevant fusion proteins for cancer therapy. International Journal of Biological Macromolecules, 187, 24-34. [CrossRef]
  • 8. Adamczyk, Z., Pomorska, A., Nattich-Rak, M., Wytrwal-Sarna, M., Bernasik, A. (2018). Protein adsorption mechanisms at rough surfaces: Serum albumin at a gold substrate. Journal of Colloid and Interface Science, 530, 631-641. [CrossRef]
  • 9. Yildiz, M. (2024). Computational analysis of interactions between drugs and human serum albumin. Journal of Molecular Recognition, 37(6), e3105 [CrossRef]
  • 10. Xu, L., Yang, H., Hu, R., Liang, Y., Li, Y., Xu, W., Fan, X., Liu, Y. (2021). Comparing the interaction of four structurally similar coumarins from Fraxinus Chinensis Roxb. with HSA through multi-spectroscopic and docking studies. Journal of Molecular Liquids, 340, 117234. [CrossRef]
  • 11. Cetinkaya, A., Caglayan, M.G., Unal, M.A., Beyazkilic, P., Elbuken, C., Atici, E.B., Ozkan, S.A. (2022). Investigation of pazopanib and human serum albumin interaction using spectroscopic and molecular docking approaches. Analytica, 3(1), 144-160. [CrossRef]
  • 12. Bagheri, M., Fatemi, M.H. (2018). Fluorescence spectroscopy, molecular docking and molecular dynamic simulation studies of HSA-Aflatoxin B1 and G1 interactions. Journal of Luminescence, 202, 345-353. [CrossRef]
  • 13. Liu, Z., Huang, X., Jiang, Z., Tuo, X. (2021). Investigation of the binding properties between levamlodipine and HSA based on MCR-ALS and computer modeling. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 245, 118929. [CrossRef]
  • 14. Amir, M., Nabi, F., Mohd Fuzail Zaheer, S., Hasan Khan, R., Javed, S. (2024). Exploring the molecular basis of tucatinib interaction with human serum albumin: A spectroscopic and computational analysis. Journal of Molecular Liquids, 401, 124642. [CrossRef]
  • 15. Fan, S.H., Wang, W.Q., Zhou, Y.W., Gao, X.J., Zhang, Q., Zhang, M.H. (2024). Research on the interaction mechanism and structural changes in human serum albumin with hispidin using spectroscopy and molecular docking. Molecules, 29(3), 655. [CrossRef]
  • 16. Chenguiti, F., Bakirhan, N.K., Gozelle, M., Doulache, M., Saidat, B., Atici, E.B., Ozkan, S.A. (2024). Enzalutamide-human serum albumin interaction: Electrochemical exploration of complex formation and binding parameters. Microchemical Journal, 201, 110760. [CrossRef]
  • 17. Fu, L., Liu, X., Zhou, Q., Zhang, J., Dong, J., Wang, J. (2014). Characterization of the interactions of human serum albumin (HSA), gatifloxacin, and metronidazole using spectroscopic and electrochemical methods. Journal of Luminescence, 149, 208-214. [CrossRef]
  • 18. Jalali, E., Sargolzaei, J., Rajabi, P. (2024). Investigating the interaction between sertraline hydrochloride and human serum albumin using equilibrium dialysis and spectroscopic methods. Inorganic Chemistry Communications, 166, 112586. [CrossRef]
  • 19. Xiong, X., He, J., Yang, H., Tang, P., Tang, B., Sun, Q., Li, H. (2017). Investigation on the interaction of antibacterial drug moxifloxacin hydrochloride with human serum albumin using multi-spectroscopic approaches, molecular docking and dynamical simulation. RSC Advances, 7(77), 48942-48951. [CrossRef]
  • 20. Li, Y., He, W., Dong, Y., Sheng, F., Hu, Z. (2006). Human serum albumin interaction with formononetin studied using fluorescence anisotropy, FT-IR spectroscopy, and molecular modeling methods. Bioorganic & Medicinal Chemistry, 14(5), 1431-1436. [CrossRef]
  • 21. Caruso, Í.P., Vilegas, W., Cristante de Oliveira, L., Cornélio, M.L. (2020). Fluorescence spectroscopic and dynamics simulation studies on isoorientin binding with human serum albumin. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 228, 117738. [CrossRef]
  • 22. Gonzàlez-Jimènez, J., Frutos, G., Cayre, I. (1992). Fluorescence quenching of human serum albumin by xanthines. Biochemical Pharmacology, 44(4), 824-826. [CrossRef]
  • 23. Fan, X.Y., Zhang, Y., Wang, J., Yang, L.Y., Jiang, F.L., Liu, Y. (2014). Exploring the interaction between rotenone and human serum albumin. The Journal of Chemical Thermodynamics, 69, 186-192. [CrossRef]
  • 24. Zhang, W., Zhong, H., Zhao, P., Shen, A., Li, H., Liu, X. (2022). Carbon quantum dot fluorescent probes for food safety detection: Progress, opportunities, and challenges. Food Control, 133, 108591. [CrossRef]
  • 25. Arshad, N., Farooqi, S.I. (2018). Cyclic voltammetric DNA binding investigations on some anticancer potential metal complexes: A review. Applied Biochemistry and Biotechnology, 186(4), 1090-1110. [CrossRef]

INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES

Yıl 2025, Cilt: 49 Sayı: 3, 21 - 21

Merve Yence , Ahmet Çetinkaya , Esen Bellur Atici , Sibel A. Özkan

https://doi.org/10.33483/jfpau.1663961

Öz

Objective: This research investigated the interaction between Eltrombopag (EB) and Human Serum Albumin (HSA) by fluorescence spectroscopy and voltammetry while explaining the quenching mechanism.
Material and Method: The electrochemical studies were conducted in an acetate buffer solution (AB) at pH 4 by differential pulse voltammetry (DPV). For the fluorescence studies, EB, HSA, and a mixture of EB and HSA solutions were designed with a pH of 4.7, AB containing 20% DMSO.
Result and Discussion: The interaction between EB and HSA was examined by fluorescence and electrochemical titrations, which showed a quenching effect and peak shifting. Fluorescence titrations indicate that EB’s HSA quenching process is static and has a hypsochromic shift. Analysis of thermodynamic parameters and higher binding constants concluded a strong and spontaneous interaction. Electrochemical titrations show the intercalation of EB into HSA.

Anahtar Kelimeler

Differential pulse voltammetry drug protein interaction eltrombopag fluorescence spectroscopy human serum albumin

Teşekkür

Ahmet Cetinkaya thanks the financial support from the Scientific and Technological Research Council of Türkiye (TUBITAK) under the BIDEB/2218-National Postdoctoral Research Scholarship Program and ARDEB/1004-Center of Excellence Support Program (Project No: 20AG003).

Kaynakça

  • 1. Ahmed, S., Bashir, Q., Bassett, R., Poon, M.Y.C., Valdez, B., Konoplev, S., Alousi, A.M., Andersson, B. S., Ciurea, S., Hosing, C., Jones, R., Kebriaei, P., Khouri, I., Kim, S., Nieto, Y., Olson, A., Oran, B., Parmar, S., Qazilbash, M. H., Popat, U. (2021). Eltrombopag for post-transplantation thrombocytopenia: Results of phase II randomized, double-blind, placebo-controlled trial. Transplantation and Cellular Therapy, 27(5), 430.e1-430.e7. [CrossRef]
  • 2. Samarkandi, H., Al Nahedh, M., Alfattani, A., Alsharif, F., Bakshi, N., Rasheed, W., Alfraih, F., Alhumaid, M., Alkhudair, N., Alhayli, S., Alsaedi, H., Shaheen, M., Hanbali, A., Hashmi, S.K., Devol, E., Alseraihy, A., Alzahrani, H., Aljurf, M. (2020). Evaluation of eltrombopag in thrombocytopenia post Hematopoietic cell transplantation: Rertrospective observational trial. Hematology/Oncology and Stem Cell Therapy. [CrossRef]
  • 3. Su, M.Y., Chang, H.H., Chou, S.W., Lu, M.Y., Yang, Y.L., Lin, D.T., Lin, K.H., Jou, S.T. (2021). Role of eltrombopag in severe aplastic anemia treatment in children. Pediatrics & Neonatology, 62(6), 655-657. [CrossRef]
  • 4. Weingarten, S.J., Friedman, D., Arora, A. (2021). Eltrombopag use for refractory immune thrombocytopenia in pregnancy: A case report. Case Reports in Women’s Health, 29, e00281. [CrossRef]
  • 5. Winer, E.S., Safran, H., Karaszewska, B., Bauer, S., Khan, D., Doerfel, S., Burgess, P., Kalambakas, S., Mostafa Kamel, Y., Forget, F. (2017). Eltrombopag for thrombocytopenia in patients with advanced solid tumors receiving gemcitabine-based chemotherapy: A randomized, placebo-controlled phase 2 study. International Journal of Hematology, 106(6), 765-776. [CrossRef]
  • 6. Menezes, T.M., Neto, A.M. da S., Gubert, P., Neves, J.L. (2021). Effects of human serum albumin glycation on the interaction with the tyrosine kinase inhibitor pazopanib unveiled by multi-spectroscopic and bioinformatic tools. Journal of Molecular Liquids, 340, 116843. [CrossRef]
  • 7. Tao, H., Wang, R., Sheng, W., Zhen, Y. (2021). The development of human serum albumin-based drugs and relevant fusion proteins for cancer therapy. International Journal of Biological Macromolecules, 187, 24-34. [CrossRef]
  • 8. Adamczyk, Z., Pomorska, A., Nattich-Rak, M., Wytrwal-Sarna, M., Bernasik, A. (2018). Protein adsorption mechanisms at rough surfaces: Serum albumin at a gold substrate. Journal of Colloid and Interface Science, 530, 631-641. [CrossRef]
  • 9. Yildiz, M. (2024). Computational analysis of interactions between drugs and human serum albumin. Journal of Molecular Recognition, 37(6), e3105 [CrossRef]
  • 10. Xu, L., Yang, H., Hu, R., Liang, Y., Li, Y., Xu, W., Fan, X., Liu, Y. (2021). Comparing the interaction of four structurally similar coumarins from Fraxinus Chinensis Roxb. with HSA through multi-spectroscopic and docking studies. Journal of Molecular Liquids, 340, 117234. [CrossRef]
  • 11. Cetinkaya, A., Caglayan, M.G., Unal, M.A., Beyazkilic, P., Elbuken, C., Atici, E.B., Ozkan, S.A. (2022). Investigation of pazopanib and human serum albumin interaction using spectroscopic and molecular docking approaches. Analytica, 3(1), 144-160. [CrossRef]
  • 12. Bagheri, M., Fatemi, M.H. (2018). Fluorescence spectroscopy, molecular docking and molecular dynamic simulation studies of HSA-Aflatoxin B1 and G1 interactions. Journal of Luminescence, 202, 345-353. [CrossRef]
  • 13. Liu, Z., Huang, X., Jiang, Z., Tuo, X. (2021). Investigation of the binding properties between levamlodipine and HSA based on MCR-ALS and computer modeling. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 245, 118929. [CrossRef]
  • 14. Amir, M., Nabi, F., Mohd Fuzail Zaheer, S., Hasan Khan, R., Javed, S. (2024). Exploring the molecular basis of tucatinib interaction with human serum albumin: A spectroscopic and computational analysis. Journal of Molecular Liquids, 401, 124642. [CrossRef]
  • 15. Fan, S.H., Wang, W.Q., Zhou, Y.W., Gao, X.J., Zhang, Q., Zhang, M.H. (2024). Research on the interaction mechanism and structural changes in human serum albumin with hispidin using spectroscopy and molecular docking. Molecules, 29(3), 655. [CrossRef]
  • 16. Chenguiti, F., Bakirhan, N.K., Gozelle, M., Doulache, M., Saidat, B., Atici, E.B., Ozkan, S.A. (2024). Enzalutamide-human serum albumin interaction: Electrochemical exploration of complex formation and binding parameters. Microchemical Journal, 201, 110760. [CrossRef]
  • 17. Fu, L., Liu, X., Zhou, Q., Zhang, J., Dong, J., Wang, J. (2014). Characterization of the interactions of human serum albumin (HSA), gatifloxacin, and metronidazole using spectroscopic and electrochemical methods. Journal of Luminescence, 149, 208-214. [CrossRef]
  • 18. Jalali, E., Sargolzaei, J., Rajabi, P. (2024). Investigating the interaction between sertraline hydrochloride and human serum albumin using equilibrium dialysis and spectroscopic methods. Inorganic Chemistry Communications, 166, 112586. [CrossRef]
  • 19. Xiong, X., He, J., Yang, H., Tang, P., Tang, B., Sun, Q., Li, H. (2017). Investigation on the interaction of antibacterial drug moxifloxacin hydrochloride with human serum albumin using multi-spectroscopic approaches, molecular docking and dynamical simulation. RSC Advances, 7(77), 48942-48951. [CrossRef]
  • 20. Li, Y., He, W., Dong, Y., Sheng, F., Hu, Z. (2006). Human serum albumin interaction with formononetin studied using fluorescence anisotropy, FT-IR spectroscopy, and molecular modeling methods. Bioorganic & Medicinal Chemistry, 14(5), 1431-1436. [CrossRef]
  • 21. Caruso, Í.P., Vilegas, W., Cristante de Oliveira, L., Cornélio, M.L. (2020). Fluorescence spectroscopic and dynamics simulation studies on isoorientin binding with human serum albumin. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 228, 117738. [CrossRef]
  • 22. Gonzàlez-Jimènez, J., Frutos, G., Cayre, I. (1992). Fluorescence quenching of human serum albumin by xanthines. Biochemical Pharmacology, 44(4), 824-826. [CrossRef]
  • 23. Fan, X.Y., Zhang, Y., Wang, J., Yang, L.Y., Jiang, F.L., Liu, Y. (2014). Exploring the interaction between rotenone and human serum albumin. The Journal of Chemical Thermodynamics, 69, 186-192. [CrossRef]
  • 24. Zhang, W., Zhong, H., Zhao, P., Shen, A., Li, H., Liu, X. (2022). Carbon quantum dot fluorescent probes for food safety detection: Progress, opportunities, and challenges. Food Control, 133, 108591. [CrossRef]
  • 25. Arshad, N., Farooqi, S.I. (2018). Cyclic voltammetric DNA binding investigations on some anticancer potential metal complexes: A review. Applied Biochemistry and Biotechnology, 186(4), 1090-1110. [CrossRef]
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılıkta Analitik Kimya
Bölüm Araştırma Makalesi
Yazarlar

Merve Yence 0000-0003-4197-1009

Ahmet Çetinkaya 0000-0001-5014-0907

Esen Bellur Atici 0000-0002-4093-441X

Sibel A. Özkan 0000-0001-7494-3077

Erken Görünüm Tarihi 13 Ağustos 2025
Yayımlanma Tarihi
Gönderilme Tarihi 23 Mart 2025
Kabul Tarihi 16 Mayıs 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 49 Sayı: 3

Kaynak Göster

APA Yence, M., Çetinkaya, A., Bellur Atici, E., Özkan, S. A. (2025). INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES. Journal of Faculty of Pharmacy of Ankara University, 49(3), 21-21. https://doi.org/10.33483/jfpau.1663961
AMA Yence M, Çetinkaya A, Bellur Atici E, Özkan SA. INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES. Ankara Ecz. Fak. Derg. Ağustos 2025;49(3):21-21. doi:10.33483/jfpau.1663961
Chicago Yence, Merve, Ahmet Çetinkaya, Esen Bellur Atici, ve Sibel A. Özkan. “INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES”. Journal of Faculty of Pharmacy of Ankara University 49, sy. 3 (Ağustos 2025): 21-21. https://doi.org/10.33483/jfpau.1663961.
EndNote Yence M, Çetinkaya A, Bellur Atici E, Özkan SA (01 Ağustos 2025) INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES. Journal of Faculty of Pharmacy of Ankara University 49 3 21–21.
IEEE M. Yence, A. Çetinkaya, E. Bellur Atici, ve S. A. Özkan, “INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES”, Ankara Ecz. Fak. Derg., c. 49, sy. 3, ss. 21–21, 2025, doi: 10.33483/jfpau.1663961.
ISNAD Yence, Merve vd. “INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES”. Journal of Faculty of Pharmacy of Ankara University 49/3 (Ağustos 2025), 21-21. https://doi.org/10.33483/jfpau.1663961.
JAMA Yence M, Çetinkaya A, Bellur Atici E, Özkan SA. INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES. Ankara Ecz. Fak. Derg. 2025;49:21–21.
MLA Yence, Merve vd. “INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES”. Journal of Faculty of Pharmacy of Ankara University, c. 49, sy. 3, 2025, ss. 21-21, doi:10.33483/jfpau.1663961.
Vancouver Yence M, Çetinkaya A, Bellur Atici E, Özkan SA. INTERACTION BETWEEN ELTROMBOPAG AND HUMAN SERUM ALBUMIN: FLUORESCENCE AND ELECTROCHEMICAL STUDIES. Ankara Ecz. Fak. Derg. 2025;49(3):21-.
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Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.