A Comprehensive Study on the Binding of Anti-cancer Drug (Floxuridine) with Human Serum Albumin

Abstract

Floxuridine, FUDR, is used to treat colorectal and other cancers such as kidney and stomach cancers. Spectroscopic techniques along with molecular docking and molecular dynamic analyzes were used to evaluate the association of FUDR with human serum albumin (HSA). Our results showed that FUDR interacts with HSA via a static, exothermic, enthalpy-driven mechanism. The binding constants (K_b) of FUDR-HSA were 7.58 ± 0.63, 3.89 ± 0.32 and 2.00 ± 0.11 × 10⁴ M⁻¹ at 303, 310 and 317 K, respectively. The most important forces that were most influential in the drug-protein interaction process were van der Waals forces and hydrogen bonds. Compared with the tyrosine (Tyr), the tryptophan (Trp) residue showed a higher quenching rate suggested that Trp residue was closer to the interaction site of FUDR. The CD spectra have shown that HSA secondary structure changes to a limited extent during the FUDR interaction process. The docking analysis showed the locations of the binding sites for FUDR on HSA (locating in site I). However, despite the binding of the FUDR to albumin, changes in protein structure are limited, and it can be hoped that after delivery to the target organ, the HSA can resume its biological activity.