We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Open Drawer MenuClose Drawer Menu
Bioanalysis
BioTechniques
Future Drug Discovery
Future Medicinal Chemistry
Future Science OA
International Journal of Pharmacokinetics
Pharmaceutical Patent Analyst
Therapeutic Delivery
Short Communication

Candesartan, losartan and valsartan Zn(II) complexes interactions with bovine serum albumin

    Valeria R Martínez

    Centro de Química Inorgánica (CEQUINOR-CONICET-CICPBA-UNLP) 120 N° 1465, La Plata, 1900, Argentina

    Search for more papers by this author

    ,
    Evelina G Ferrer

    Centro de Química Inorgánica (CEQUINOR-CONICET-CICPBA-UNLP) 120 N° 1465, La Plata, 1900, Argentina

    Search for more papers by this author

    &
    Patricia AM Williams

    *Author for correspondence:

    E-mail Address: williams@quimica.unlp.edu.ar

    Centro de Química Inorgánica (CEQUINOR-CONICET-CICPBA-UNLP) 120 N° 1465, La Plata, 1900, Argentina

    Search for more papers by this author

    Published Online:3 Nov 2021https://doi.org/10.4155/fmc-2021-0216

    Abstract

    Background: The pharmacological response and the therapeutic efficacy of a drug depends on the interactions with plasma proteins. Methodology: The interaction of bovine serum albumin (BSA) with the metal complexes of antihypertensive drugs, Zn(II)/sartan complexes (candesartan, valsartan and losartan), was investigated using fluorescence quenching determinations at different temperatures. Results: The binding studies of the compounds with BSA showed static quenching and moderate binding with calculated constants in the range of 104–106 M-1, indicating potent serum distribution via albumins. In all cases, negative values of free energy are indicative of spontaneous processes and the stabilization of BSA/compound complexes through hydrogen bonding and van der Waals forces. The results for the sartans agree with the reported pharmacokinetics studies. Conclusion: It has been determined that the three sartans and the Zn complexes could be transported and distributed by albumin.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest

    References

    • 1. Friedrichs B, Peters TH Jr. All about albumin: biochemistry, genetics, and medical applications. Food / Nahrung 41(6), 382–382 (1997).
      Google Scholar
    • 2. Chadborn N, Bryant J, Bain AJ, O'Shea P. Ligand-dependent conformational equilibria of serum albumin revealed by tryptophan fluorescence quenching. Biophys. J. 76(4), 2198–2207 (1999).
      Medline CASGoogle Scholar
    • 3. Peters T. Serum albumin. Adv. Protein Chem. 37(C), 161–245 (1985).
      Medline CASGoogle Scholar
    • 4. Majorek KA, Porebski PJ, Dayal A et al. Structural and immunologic characterization of bovine, horse, and rabbit serum albumins. Mol. Immunol. 52(3–4), 174–182 (2012). • Describes the structure of different serum albumins.
      Medline CASGoogle Scholar
    • 5. Takezako T, Unal H, Karnik SS, Node K. Current topics in angiotensin II type 1 receptor research: focus on inverse agonism, receptor dimerization and biased agonism. Pharmacol. Res. 123, 40–50 (2017).
      Medline CASGoogle Scholar
    • 6. Tomat AL, Costa M de los Á, Arranz CT. Zinc restriction during different periods of life: influence in renal and cardiovascular diseases. Nutrition 27(4), 392–398 (2011).
      Medline CASGoogle Scholar
    • 7. Martínez V, Aguirre MV, Todaro JS et al. Interaction of Zn with losartan: activation of intrinsic apoptotic signaling pathway in lung cancer cells and effects on alkaline and acid phosphatases. Biol. Trace Elem. Res. 186(2), 413–429 (2018).
      Medline CASGoogle Scholar
    • 8. Martínez V, Aguirre MV, Todaro JS et al. Azilsartan and its Zn(II) complex: synthesis, anticancer mechanisms of action and binding to bovine serum albumin. Toxicol. Vitr. 48, 205–220 (2018).
      Medline CASGoogle Scholar
    • 9. Martínez VR, Aguirre MV, Todaro JS, Ferrer EG, Williams PAM. Improvement of the anticancer activities of telmisartan by Zn(II) complexation and mechanisms of action. Biol. Trace Elem. Res. 197(2), 454–463 (2020).
      Medline CASGoogle Scholar
    • 10. Martínez VR, Aguirre MV, Todaro JS, Ferrer EG, Williams PAM. Candesartan and valsartan Zn(ii) complexes as inducing agents of reductive stress: mitochondrial dysfunction and apoptosis. New J. Chem. 45(2), 939–951 (2021).
      CASGoogle Scholar
    • 11. Martínez VR, Aguirre MV, Todaro JS et al. Zinc complexation improves angiotensin II receptor type 1 blockade and in vivo antihypertensive activity of telmisartan. Future Med. Chem. 13(1), 13–23 (2021).
      CASGoogle Scholar
    • 12. Bi S, Sun Y, Qiao C, Zhang H, Liu C. Binding of several anti-tumor drugs to bovine serum albumin: fluorescence study. J. Lumin. 129(5), 541–547 (2009).
      CASGoogle Scholar
    • 13. Ashoka S, Seetharamappa J, Kandagal PB, Shaikh SMT. Investigation of the interaction between trazodone hydrochloride and bovine serum albumin. J. Lumin. 121(1), 179–186 (2006).
      CASGoogle Scholar
    • 14. Topală T, Bodoki A, Oprean L, Oprean R. Bovine serum albumin interactions with metal complexes. Med. Pharm. Reports. 87(4), 215–219 (2014).
      Google Scholar
    • 15. Makarska-Bialokoz M. Interactions of hemin with bovine serum albumin and human hemoglobin: a fluorescence quenching study. Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 193, 23–32 (2018).
      Medline CASGoogle Scholar
    • 16. Meti MD, Nandibewoor ST, Joshi SD, More UA, Chimatadar SA. Multi-spectroscopic investigation of the binding interaction of fosfomycin with bovine serum albumin. J. Pharm. Anal. 5(4), 249–255 (2015).
      Medline CASGoogle Scholar
    • 17. Shi JH, Wang J, Zhu YY, Chen J. Characterization of interaction between isoliquiritigenin and bovine serum albumin: spectroscopic and molecular docking methods. J. Lumin. 145, 643–650 (2014).
      CASGoogle Scholar
    • 18. Lakowicz JR. Principles of fluorescence spectroscopy. Springer Science & Business Media, NY, USA (2013). • Gives an introduction to the biophysical principles of fluorescence methods.
      Google Scholar
    • 19. Wang BL, Pan DQ, Zhou KL, Lou YY, Shi JH. Multi-spectroscopic approaches and molecular simulation research of the intermolecular interaction between the angiotensin-converting enzyme inhibitor (ACE inhibitor) benazepril and bovine serum albumin (BSA). Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 212, 15–24 (2019).
      Medline CASGoogle Scholar
    • 20. Wang Q, Huang CR, Jiang M et al. Binding interaction of atorvastatin with bovine serum albumin: spectroscopic methods and molecular docking. Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 156, 155–163 (2016).
      Medline CASGoogle Scholar
    • 21. Zhang YF, Zhou KL, Lou YY, Pan DQ, Shi JH. Investigation of the binding interaction between estazolam and bovine serum albumin: multi-spectroscopic methods and molecular docking technique. J. Biomol. Struct. Dyn. 35(16), 3605–3614 (2017).
      Medline CASGoogle Scholar
    • 22. Fraiji LK, Hayes DM, Werner TC. Static and dynamic fluorescence quenching experiments for the physical chemistry laboratory. J. Chem. Educ. 69(5), 424–428 (1992).
      CASGoogle Scholar
    • 23. Kou SB, Lin ZY, Wang BL, Shi JH, Liu YX. Evaluation of the binding behavior of olmutinib (HM61713) with model transport protein: insights from spectroscopic and molecular docking studies. J. Mol. Struct. 1224(129024), 1–11 (2021).
      Google Scholar
    • 24. Pawar S, Joshi R, Ottoor D. Spectroscopic and molecular docking study to understand the binding interaction of rosiglitazone with bovine serum albumin in presence of valsartan. J. Lumin. 197, 200–210 (2018).
      CASGoogle Scholar
    • 25. Sun H, Science E, Science A. Spectrofluorimetric study on the interaction of losartan potassium. Int. J. Pharm. Sci. Res. 7(3), 1026–1034 (2016).
      Google Scholar
    • 26. Tarushi A, Kastanias P, Raptopoulou CP et al. Zinc complexes of flufenamic acid: characterization and biological evaluation. J. Inorg. Biochem. 163, 332–345 (2016).
      Medline CASGoogle Scholar
    • 27. Tolia C, Papadopoulos AN, Raptopoulou CP et al. Copper(II) interacting with the non-steroidal antiinflammatory drug flufenamic acid: structure, antioxidant activity and binding to DNA and albumins. J. Inorg. Biochem. 123, 53–65 (2013).
      Medline CASGoogle Scholar
    • 28. Escudero GE, Laino CH, Martini N. Zn(II) based potential drug containing sertraline as a strong antidepressant agent. Ann. Med. Chem. Res. 3(1), 1017 (2017).
      Google Scholar
    • 29. Ross PD, Subramanian S. Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20(11), 3096–3102 (1981).
      Medline CASGoogle Scholar
    • 30. Fu XB, Lin ZH, Liu HF, Le XY. A new ternary copper(II) complex derived from 2-(2′-pyridyl)benzimidazole and glycylglycine: synthesis, characterization, DNA binding and cleavage, antioxidation and HSA interaction. Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 122, 22–33 (2014).
      Medline CASGoogle Scholar
    • 31. Husain A, Azim S, Mitra M, Bhasin PS. A review on candesartan: pharmacological and pharmaceutical profile. J. Appl. Pharm. Sci. 01(10), 12–17 (2011). • Reports pharmacokinetics studies of some angiotensin receptor blockers.
      Google Scholar