Spectroscopic studies on binding of ibuprofen and drotaverine with bovine serum albumin

Abstract

The interaction between ibuprofen (analgesic) and drotaverine (smooth muscle relaxant) drugs with bovine serum albumin (BSA) was investigated using both experimental (UV–Vis, fluorescence, and circular dichroism spectroscopy) and theoretical (molecular mechanics) methods. Both drugs quench the intrinsic fluorescence of BSA through static processes. The binding constant of the BSA–drotaverine complex is found to be relatively higher than that of the BSA–ibuprofen complex. The binding distance between BSA and ibuprofen/drotaverine was calculated to be 1.7 and 3.1 nm, respectively. Both fluorescence and circular dichroism spectral studies confirmed conformational changes in the BSA upon binding with these drugs. From both displacement competition studies and molecular docking, it was found that drotaverine can displace ibuprofen at higher concentrations, but ibuprofen can bind to other sites on the BSA. Circular dichroism showed that drotaverine has a stabilizing effect on the secondary structure of BSA in the presence of ibuprofen, which on its own leads to an increase in the disordered fraction at high concentrations.These observations imply that concurrent administration of these two drugs can be effective as a combination therapy in the management of pain due to primary dysmenorrhea, even when the disease tends to gain resistance to the NSAIDs; their competition for the BSA binding sites should be taken into account.