RESUMEN
Acetylcholinesterase (AChE) inhibitors cause insect death by preventing the hydrolysis of the neurotransmitter acetylcholine, which overstimulates the nervous system. In this study, isorhapontin, isolated from E. globulus leaves, was evaluated as a natural insecticide with AChE inhibition at 12.5 µM. Using kinetic analyses, we found that isorhapontin acted as a competitive inhibitor that binds to the active site of AChE. The inhibition constant (Ki) was 6.1 µM. Furthermore, isorhapontin and resveratrol, which have basic skeletons, were predicted to bind to the active site of AChE via molecular docking. A comparison of the hydrogen bonding between the two stilbenes revealed characteristic differences in their interactions with amino acids. In isorhapontin, Trp83, Gly149, Tyr162, Tyr324, and Tyr370 interacted with the sugar moiety. These results suggest that with further development, isorhapontin can be used as an insecticide alternative.
Asunto(s)
Eucalyptus , Insecticidas , Estilbenos , Acetilcolinesterasa/metabolismo , Insecticidas/farmacología , Simulación del Acoplamiento Molecular , Eucalyptus/metabolismo , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Hojas de la Planta/metabolismoRESUMEN
This study aimed to isolate bacterial neuraminidase (BNA) inhibitory O-methylated quercetin derivatives from the aerial parts of S. pubescens. All the isolated compounds were identified as O-methylated quercetin (1-4), which were exhibited to be noncompetitive inhibitors against BNA, with IC50 ranging from 14.0 to 84.1 µM. The responsible compounds (1-4) showed a significant correlation between BNA inhibitory effects and the number of O-methyl groups on quercetin; mono (1, IC50 = 14.0 µM) > di (2 and 3, IC50 = 24.3 and 25.8 µM) > tri (4, IC50 = 84.1 µM). In addition, the binding affinities between BNA and inhibitors (1-4) were also examined by fluorescence quenching effect with the related constants (KSV, KA, and n). The most active inhibitor 1 possessed a KSV with 0.0252 × 105 L mol-1. Furthermore, the relative distribution of BNA inhibitory O-methylated quercetins (1-4) in S. pubescens extract was evaluated using LC-Q-TOF/MS analysis.