N-ethyl-2-pyrrolidinone substitution enhances binding affinity between tea flavoalkaloids and human serum albumin: Greatly influenced by esterization.

Formation of catechins-human serum albumin (HSA) complex contributes to stably transporting catechins and regulating their bioavailability. Recently, a new class of catechins namely flavoalkaloids have been reported from tea. The unique structural modification with an N-ethyl-2-pyrrolidinone ring at catechins from these flavoalkaloids has raised our interest in their HSA binding affinity. Thus, we investigated the interaction between HSA and flavoalkaloids by molecular docking, UV-Vis spectroscopy (UV), fluorescence quenching approaches, and surface plasmon resonance (SPR). Thermodynamic parameters suggest that electrostatic forces contribute greatly to the interaction. The binding ability is affected by different ester group (galloyl or cinnamoyl) at 3-OH, N-ethyl-2-pyrrolidinone substituted position (C-6 or C-8), C-2, C-3 and C-5''' configurations, and hydroxyl group numbers at B ring, among which the 3-O-cinnamoyl substitution and 5'''-R configuration present the strongest contributions. UV showed slight changes in the conformation and microenvironment of HSA during the binding process. The quenching and binding constants suggest that the quenching is a static type. The small K values (1-20 μM) detected by SPR confirmed the strong binding affinities between HSA and flavoalkaloids. Present study will help us to understand the interaction mechanism between flavoalkaloids and HSA, shedding light on structural modification of common catechins to enhance the stability, bioavailability and bioactivities.