Comparative study of the interaction mechanism of astilbin, isoastilbin, neoastilbin with CYP3A4.

Abstract

The interactions of human CYP3A4 with three selected isomer flavonoids, such as astilbin, isoastilbin and neoastilbin, are clarified using spectral analysis, molecular docking and molecular dynamics simulation. During binding with the three flavonoids, the intrinsic fluorescence of CYP3A4 is statically quenched in static mode with non-radiative energy conversion. The fluorescence and UV/Vis data reveal that the three flavonoids have moderate and stronger binding affinity with CYP3A4 due to the order of Ka1 and Ka2 values ranged from 104 to 105 L·mol-1 . In the meantime, astilbin has the highest affinity with CYP3A4, then isoastilbin and neoastilbin at the three experimental temperatures. Multispectral analysis confirms that the binding of the three flavonoids results in clear changes in the secondary structure of CYP3A4. It can be found from fluorescence, UV/Vis and molecular docking that these three flavonoids strongly bind to CYP3A4 by the means of hydrogen bond and van der Waals forces. The key amino acids around the binding site are also elucidated. Furthermore, the stabilities of the three-CYP3A4 complexes are evaluated by molecular dynamics simulation.