Title
Kolaflavanone of kolaviron selectively binds to subdomain 1B of human serum albumin: spectroscopic and molecular docking evidences
Author
Ayodele O. Kolawole, Adejoke N. Kolawole, Kolawole A. Olofinsan, Olusola O. Elekofehinti
Year
2020
Journal
Computational Toxicology
Abstract
Human serum albumin (HSA) is involved in transporting a wide range of therapeutic agents. This involvement determines the pharmacokinetics and pharmacodynamic properties of the compounds. The interaction of kolaflavanone, a component of kolaviron complex, a therapeutic flavonoid isolated from Garcinia kola (Bitter kola), with human serum albumin (HSA) was studied using various spectroscopic and in silico approaches. Kolaflavanone quenched the intrinsic fluorescence of HSA and the quenching constant was of the order of 10 L. mol. The quenching mechanism was a static process. HSA has one binding site for kolaflavanone and displayed a very rapid pharmacokinetic-pharmacodynamic time for bioflavonoid characterised by low bioavailability. At the simulative physiological condition, van der Waals forces and hydrogen bond were primarily involved in the association process. The interaction was exothermic; and enthalpic driven. Hydrophobic interaction was obvious at pH 5.0 and 9.0. The interaction caused a slight change in HSA α-helical content without perturbing the intrinsic fluorophore microenvironment. The displacement experiment and molecular docking proposed that kolaflavanone is preferentially bound to HSA subdomain 1B. Kolaflavanone in vivo bioavailability could be limited by temperature and viscosity induced crowder. Molecular dynamics studies showed that the complex attained equilibrium during simulation, indicating the stability of the HSA-kolaflavanone complex despite slight perturbation.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Tertiary structure, Ligand binding, Biochemistry