RESUMEN
The inhibition of α-glucosidase activity is a prospective approach to prevent postprandial hyperglycemia. As two flavonoids extracted from citrus fruits, eriocitrin and eriodictyol have similar structures and show multiple pharmacological activities. In order to investigate the effects of flavonoids structure on enzyme inhibition, spectroscopy and molecular docking analysis were used. Saccharomyces cerevisiae α-glucosidase (GH13) was used for studying the inhibitory mechanism by multi-spectroscopic analysis. Results indicated that they could quench the intrinsic fluorescence of α-glucosidase, the binding constants at 298 K were (7.02 ± 0.22) × 104 and (4.57 ± 0.16) × 104 L mol-1, respectively. The interaction between them with α-glucosidase were mainly driven by hydrophobic interaction, they induced conformational changes of α-glucosidase. The human α-glucosidase (C-terminal maltase-glucoamylase, GH31) was used in the molecular docking analysis to determine the interaction of eriocitrin and eriodictyol with the α-glucosidase. The results revealed that they could bind with α-glucosidase and might cause the decrease of α-glucosidase activity. The inhibitory effect of eriocitrin was stronger than that of eriodictyol, which might be due to the position and amount of hydroxyl groups. This work confirmed two novel α-glucosidase inhibitors and provided the structure-function relationship of flavonoids in inhibition of α-glucosidase activity.
Asunto(s)
Flavonoides/química , Flavonoides/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Simulación del Acoplamiento Molecular , alfa-Glucosidasas/metabolismo , Flavonoides/metabolismo , Inhibidores de Glicósido Hidrolasas/metabolismo , Humanos , Conformación Proteica , Análisis Espectral , alfa-Glucosidasas/químicaRESUMEN
This study aims to investigate the interaction between fluoranthene (FLA) and Bovine hemoglobin (BHb) by ultraviolet-visible (UV-vis) absorption, fluorescence, synchronous fluorescence, circular dichroism (CD) spectroscopy and molecular docking method. The results showed that the fluorescence intensity of BHb was declined with the increase of FLA concentration. The binding procedure was spontaneous mainly driven by hydrophobic force. The number of binding sites were 0.709 (298â¯K), and 1.41 (310â¯K). The binding constants were equal to 4.68â¯×â¯103â¯mol·L-1 at 298â¯K and 6.17â¯×â¯105â¯mol·L-1 at 310â¯K. The binding distance between FLA and the tryptophan residue of BHb was 4.50â¯nm. The results of UV-vis spectra, synchronous fluorescence and CD spectra revealed that FLA could change the conformation of BHb, which might affect the physiological functions of hemoglobin. Moreover, molecular modeling results showed that the fluorescence experimental results were in agreement with the results obtained by molecular docking.