Interaction Studies of Vinblastine Drug with Human Serum Albumin (HSA) by Spectroscopic and Molecular Modeling Studies

Abstract

Background: The interactions of anticancer drugs with blood plasma constituents, particularly with human serum albumin (HSA) have a major influence on drug pharmacology and efficacy in overcoming the biological barriers to drug delivery and the targeting of active drugs to their specific site of action. Aim: to examine the interaction of vinblastine with human serum albumin (HSA) by means of various spectroscopic method (viz: UV/visible) in combination with molecular docking techniques. Methods: HSA was purchased from Sigma and used without further purification. Vinblastine, Tris(hydroxymethyl) aminomethane or Tris Buffer (Sigma), were used as received. Doubly distilled water was used as the solvent throughout the experiments. All reagents were of the best commercial grade and were used without further purification. Human serum albumin of 1×10-3 M was prepared by dissolving protein in Tris-HCl buffer solution at pH 7.4. Results: The results of fluorescence measurements indicate that Vinblastine has a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. The binding constants (K) at different temperatures and thermodynamic parameters, enthalpy changes (ΔH) and entropy changes (ΔS) were calculated according to the fluorescence data. Furthermore, molecular docking studies revealed that the, Vinblastine was located to the entrance of site I by electrostatic and hydrophobic forces, which matched exactly with the corresponding experimental results. Conclusion: All the experimental results and theoretical data indicated that Vinblastine drug bound to HSA and was effectively transported and eliminated in the body. Such findings may provide useful guidelines for further drug design