The binding interaction between clofarabine, an important anticancer drug and two important carrier proteins
found abundantly in human plasma, Human Serum Albumin (HSA) and α-1 acid glycoprotein (AAG) was investi
gated by spectroscopic and molecular modeling methods. The results obtained from fluorescence quenching ex
periments demonstrated that the fluorescence intensity of HSA and AAG is quenched by clofarabine and the static
mode of fluorescence quenching is operative. UV–vis spectroscopy deciphered the formation of ground state com
plex between anticancer drug and the two studied proteins. Clofarabine was found to bind at 298 K with both
AAG and HSA with the binding constant of 8.128 × 10 and 4.120 × 10 for AAG and HSA, respectively. There is
stronger interaction of clofarabine with AAG as compared to HSA. The Gibbs free energy change was found to
be negative for the interaction of clofarabine with AAG and HSA indicating that the binding process is sponta
neous. Binding of clofarabine with HSA and AAG induced ordered structures in both proteins and lead to molec
ular compaction. Clofarabine binds to HSA near to drug site II. Hydrogen bonding and hydrophobic interactions
were the main bonding forces between HSA-clofarabine and AAG-clofarabine as revealed by docking results.
This study suggests the importance of binding of anticancer drug to AAG spatially in the diseases like cancers where the plasma concentration of AAG increases many folds. Design of drug dosage can be adjusted accordingly to achieve optimal treatment outcome.