Influence of the caffeine on the interaction Between haloperidol and human serum albumin: Spectroscopic and molecular docking approach

Abstract

The interactions between human serum albumin (HSA) and haloperidol (HPD) in the presence or absence of caffeine (CAF) with HSA were studied by fluorescence-absorption spectroscopy and molecular modeling. The results showed that the presence of CAF decreased binding constants of HPD HSA with increasing temperature from 1.07× 104 mol/dm3 to 3.13 x 102 mol/dm3. The results indicate that the HSA-HPD and HSA-CAF-HPD system is very thermally sensitive. The number of binding sites obtained at three different temperatures were close to 1 indicating the presence of one binding site of HPD, CAF on HSA. Fluorescence quenching was initiated by dynamic quenching procedure irrespective of the absence or presence of CAF. The negative value of the free energy change (∆G) indicates a spontaneous binding process of both, HPD to HSA protein and HPD to the HSA-CAF protein complex. The values of ∆H0 <0 and ∆S0 <0 for binding interaction HSA-HPD and HSA-CAF HPD, indicate that interaction is enthalpy driven. Docking simulation results are confirmed that the most preferable place for binding HPD and CAF is the active site I, in domain II subdomain IIA. The present study suggested that the combined actions of HPD and CAF, may lead to further changes in HSA conformation.