Interaction of 5-Fluorouracil and its derivatives with bovine serum albumin

Fluorouracil (5-FU) and its derivatives are the most commonly used drugs to treat many types of cancer. Two dual functional agents, FUPAE and FUPAP, derived from 5-Fluorouracil (5-FU) have shown radiosensitizing activity but unlike their components were not cytotoxic. This study was designed to examine the interaction of BSA with 5-Fluorouracil (5-FU) and two of its derivatives; FUPAE and FUPAP at physiological conditions, using a constant protein concentration and various drug contents. FTIR, UV–Vis spectroscopic methods as well as molecular modelling were used to determine the drugs binding mode, the binding constants and the effects of drug complexation on BSA stability and conformation. Structural analysis showed that 5-Fluorouracil, FUPAE and FUPAP bind BSA via polypeptide polar groups with overall binding constants of K5-FU–BSA = 3.02(±0.09) × 103, KFUPAE–BSA = 1.08(±0.04) × 104, KFUPAP–BSA = 1.21(±0.06) × 104 M−1. BSA conformation was altered by a major reduction of α-helix from 69% (free BSA) to 34% with 5-FU, 40% with FUPAE, 38% with FUPAP. These results suggest that serum albumins might act as carrier proteins for FUPAE and FUPAP in delivering them to target tissues.

Figure optionsDownload as PowerPoint slideHighlights
► 5-Fluorouracil, FUPAE and FUPAP bind BSA via polypeptide polar groups.
► FUPAE and FUPAP mainly interact with the positively charged amino acids.
► The stronger binding was observed for FUPAP and FUPAP than 5-FU.
► BSA can be considered as a good carrier for transportation of FUPAE and FUPAP in vivo.