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

[Image: see text] 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 × 10(5) 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.