Elucidating the Interactions of Fluoxetine with Human Transferrin Employing Spectroscopic, Calorimetric, and In Silico Approaches: Implications of a Potent Alzheimer's Drug

Mohd Shahnawaz Khan; Moyad Shahwan; Anas Shamsi; Fahad A Alhumaydhi; Suliman A Alsagaby; Waleed Al Abdulmonem; Bekhzod Abdullaev; Dharmendra Kumar Yadav

doi:10.1021/acsomega.2c00182

Elucidating the Interactions of Fluoxetine with Human Transferrin Employing Spectroscopic, Calorimetric, and In Silico Approaches: Implications of a Potent Alzheimer's Drug

ACS Omega. 2022 Mar 2;7(10):9015-9023. doi: 10.1021/acsomega.2c00182. eCollection 2022 Mar 15.

Authors

Mohd Shahnawaz Khan¹, Moyad Shahwan^{2

3}, Anas Shamsi^{3

4}, Fahad A Alhumaydhi⁵, Suliman A Alsagaby⁶, Waleed Al Abdulmonem⁷, Bekhzod Abdullaev⁸, Dharmendra Kumar Yadav⁹

Affiliations

¹ Department of Biochemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
² College of Pharmacy & Health Sciences, Ajman University, Ajman 346, United Arab Emirates.
³ Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates.
⁴ Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
⁵ Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.
⁶ Department of Medical Laboratories Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11932, Saudi Arabia.
⁷ Department of Pathology, College of Medicine, Qassim University, Buraydah 51452, Saudi Arabia.
⁸ Scientific Department, Akfa University, Tashkent 100095, Uzbekistan.
⁹ College of Pharmacy, Gachon University of Medicine and Science, Hambakmoeiro, Yeonsu-gu, Incheon City 21924, South Korea.

Abstract

Neurodegenerative complexities, such as dementia, Alzheimer's disease (AD), and so forth, have been a crucial health concern for ages. Transferrin (Tf) is a chief target to explore in AD management. Fluoxetine (FXT) presents itself as a potent anti-AD drug-like compound and has been explored against several diseases based on the drug repurposing readings. The present study delineates the binding of FXT to Tf employing structure-based docking, molecular dynamics (MD) simulations, and principal component analysis (PCA). Docking results showed the binding of FXT with Tf with an appreciable binding affinity, making various close interactions. MD simulation of FXT with Tf for 100 ns suggested their stable binding without any significant structural alteration. Furthermore, fluorescence-based binding revealed a significant interaction between FXT and Tf. FXT binds to Tf with a binding constant of 5.5 × 10⁵ M^-1. Isothermal titration calorimetry (ITC) advocated the binding of FXT to Tf as spontaneous in nature, affirming earlier observations. This work indicated plausible interactions between FXT and Tf, which are worth considering for further studies in the clinical management of neurological disorders, including AD.