Exploring the binding mechanism of ondansetron hydrochloride to serum albumins: Spectroscopic approach

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Molecular and biomolecular spectroscopy, 2012-02, Vol.86, p.410-416
• Main Authors: B., Sandhya, Hegde, Ashwini H., K.C., Ramesh, J., Seetharamappa
• Format: Article
• Language: English
• Subjects: Conformational changes; Interactions; Ondansetron hydrochloride; Serum albumins
• ISSN: 1386-1425
• DOI: 10.1016/j.saa.2011.10.060

The interaction of ondansetron hydrochloride (OND) with serum albumins (BSA and HSA) was studied by spectroscopic methods. The binding characteristics and thermodynamics parameters were evaluated and the mode of binding was proposed. The three dimensional fluorescence spectra revealed that the interaction between OND and protein caused conformational and microenvironmental alterations in the protein molecule. [Display omitted] ► We explored the interaction of serum albumins (BSA and HSA) with ondansetron hydrochloride (OND) by spectroscopic methods. ► The quenching mechanism is static quenching mechanism. ► The interaction is driven mainly by both hydrogen bond and hydrophobic interactions and OND bound to albumins at subdomin II A. ► The presence of metal ions influenced the binding of OND–protein complex. ► Different spectroscopic studies revealed the changes in the secondary structure of protein upon interaction with OND. The mechanism of interaction of ondansetron hydrochloride (OND) to serum albumins [bovine serum albumin (BSA) and human serum albumin (HSA)] was studied for the first time employing fluorimetric, circular dichroism, FTIR and UV–vis absorption techniques under the simulated physiological conditions. Fluorimetric results were utilized to investigate the binding and conformational characteristics of protein upon interaction with varying concentrations of the drug. Higher binding constant values revealed the strong interaction between the drug and protein while the number of binding sites close to unity indicated single class of binding site for OND in protein. Thermodynamic results revealed that both hydrogen bond and hydrophobic interactions played a major role in stabilizing drug–protein complex. Site marker competitive experiments indicated that the OND bound to albumins at subdomin II A (Sudlow's site I). Further, the binding distance between OND and serum albumin was calculated based on the Förster's theory of non-radioactive energy transfer and found to be 2.30 and 3.41 nm, respectively for OND–BSA and OND–HSA. The circular dichroism data revealed that the presence of OND decreased the α-helix content of serum albumins. 3D-fluorescence results also indicated the conformational changes in protein upon interaction with OND. Further, the effects of some cations have been investigated in the interaction of drug to protein.