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Investigation of Atorvastatin interaction with human serum albumin: evaluation of pH effect and competitive binding with warfarin

Year 2022, Volume: 26 Issue: 5, 1386 - 1402, 28.06.2025

Hossein Haghaei Sheida Norouzi Mostafa Zakariazadeh Somaieh Soltani

Abstract

The current research used a fluorescence quenching titrations method combined with UV-Vis and FTIR-ATR spectroscopy to investigate the molecular mechanism of atorvastatin interaction with human serum albumin (HSA). Thermodynamic evaluations and molecular docking simulations were used to investigate the mode of atorvastatin-HSA interaction and the contributed intramolecular forces in complex stabilization. Atorvastatin is a statin anti-lipid drug that has recently sparked interest due to its growth-factor-like properties and other pharmacological functions, necessitating detailed knowledge of its molecular mechanism of action. UV-Vis spectra analysis confirmed the formation of the HSA-atorvastatin complex while fitting the fluorescence quenching titrations data to the proper models revealed that complex formation is facilitated by a combined static and dynamic mechanism with a quenching constant value (KSV) of 2.25×104 M-1 at 298 K. FTIR studies showed the variation of the secondary structure of the HSA due to the complex formation with atorvastatin. Based on the thermodynamic evaluations, the complex formation probability was increased due to the improved diffusion and miscibility or conformational change of HSA. Although hydrophobic interactions contribute to atorvastatin-HSA complex formation. Decreased binding was observed both in acidic and basic pHs, which could be a result of variation in the contribution of COOH moiety of atorvastatin in complex formation at different pH. Molecular docking simulations confirmed competitive binding of atorvastatin and warfarin to the site I of HSA. The docking results revealed that the flexibility of the atorvastatin molecular structure is critical in improving the stability of the atorvastatin-HSA complex.

Keywords

Atorvastatin Human Serum Albumin (HSA) Spectroscopy Molecular Docking Drug-protein binding

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There are 59 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Chemistry
Journal Section Articles
Authors

Hossein Haghaei 0000-0001-9453-0886

Sheida Norouzi 0000-0002-7551-1396

Mostafa Zakariazadeh 0000-0003-3247-3876

Somaieh Soltani 0000-0002-0102-2960

Publication Date June 28, 2025
Published in Issue Year 2022 Volume: 26 Issue: 5

Cite

APA Haghaei, H., Norouzi, S., Zakariazadeh, M., Soltani, S. (2025). Investigation of Atorvastatin interaction with human serum albumin: evaluation of pH effect and competitive binding with warfarin. Journal of Research in Pharmacy, 26(5), 1386-1402.
AMA Haghaei H, Norouzi S, Zakariazadeh M, Soltani S. Investigation of Atorvastatin interaction with human serum albumin: evaluation of pH effect and competitive binding with warfarin. J. Res. Pharm. June 2025;26(5):1386-1402.
Chicago Haghaei, Hossein, Sheida Norouzi, Mostafa Zakariazadeh, and Somaieh Soltani. “Investigation of Atorvastatin Interaction With Human Serum Albumin: Evaluation of PH Effect and Competitive Binding With Warfarin”. Journal of Research in Pharmacy 26, no. 5 (June 2025): 1386-1402.
EndNote Haghaei H, Norouzi S, Zakariazadeh M, Soltani S (June 1, 2025) Investigation of Atorvastatin interaction with human serum albumin: evaluation of pH effect and competitive binding with warfarin. Journal of Research in Pharmacy 26 5 1386–1402.
IEEE H. Haghaei, S. Norouzi, M. Zakariazadeh, and S. Soltani, “Investigation of Atorvastatin interaction with human serum albumin: evaluation of pH effect and competitive binding with warfarin”, J. Res. Pharm., vol. 26, no. 5, pp. 1386–1402, 2025.
ISNAD Haghaei, Hossein et al. “Investigation of Atorvastatin Interaction With Human Serum Albumin: Evaluation of PH Effect and Competitive Binding With Warfarin”. Journal of Research in Pharmacy 26/5 (June 2025), 1386-1402.
JAMA Haghaei H, Norouzi S, Zakariazadeh M, Soltani S. Investigation of Atorvastatin interaction with human serum albumin: evaluation of pH effect and competitive binding with warfarin. J. Res. Pharm. 2025;26:1386–1402.
MLA Haghaei, Hossein et al. “Investigation of Atorvastatin Interaction With Human Serum Albumin: Evaluation of PH Effect and Competitive Binding With Warfarin”. Journal of Research in Pharmacy, vol. 26, no. 5, 2025, pp. 1386-02.
Vancouver Haghaei H, Norouzi S, Zakariazadeh M, Soltani S. Investigation of Atorvastatin interaction with human serum albumin: evaluation of pH effect and competitive binding with warfarin. J. Res. Pharm. 2025;26(5):1386-402.