Preferential Binding of Flavonoids with Bovine Serum Albumin: In-Silico and Spectroscopic Insight into Cytotoxic Competence

Abstract

Flavonoids are polyphenolic secondary metabolites with numerous pharmacological advantages including their competence as anticancer molecules. Flavopiridol (FLAP) and riviciclib (RCB) are semi-synthetic analogs of a natural flavonoid rohitukine, isolated from the stem bark of an Indian medicinal plant, Dysoxylum binectariferum. These are cyclin-dependent kinase inhibitors (CDKIs), however, their specificity for biomolecules and mechanism of inhibition inside cell is not well deciphered. Considering the significance these inhibitors in cancer therapeutics, herein, we explored the molecular interaction mechanism between FLAP/RCB and bovine serum albumin (BSA) using various spectroscopic and molecular docking methods. Surface enhanced Raman, circular dichroism and absorption spectroscopy have been employed to understand the structural-conformational aspects and other binding parameters between FLAP/RCB and BSA. Vibrational spectroscopic studies reveal that interacts with the amino acid residues of BSA without interrupting with the microenvironment of around the residue Trp213. Further, the FLAP-BSA interactions are stabilized by hydrophobic and electrostatic forces, whereas, hydrophobic interactions are observed for binding between RCB and BSA. Comparative experimental results illustrate that the primary binding sites for FLAP and RCB on BSA are sites II and III. Conformationally, there is reduction in alpha-helical content of BSA, when complexed with FLAP/RCB indicating partial unfolding of BSA and increase in the turns and random coil structures of protein. The binding constant (Ka) estimated for the complexation is of the order of 105 and 104 for FLAP/RCB-BSA complexes respectively, specifying moderate to strong binding affinity. Further, molecular docking simulations have been performed, which are in corroboration with spectroscopic outcomes. Hence, the findings concluded here, paves a way in delineating the action mechanism of flavonoids that may lead to rational designing of flavonoid based new therapeutics and recognizing BSA as molecular target.