RESUMO
An acetylcholinesterase inhibitory compound was isolated from Tephrosia purpurea (L.) Pers. by zebrafish brain based bioassay guided isolation and predicted as trans-tephrostachin.Enzyme kinetics studies (Line weaver-Burk plots and Michaelis Menten equation) favored the reversible / mixed type, with the inhibition constant (Ki) of 53.0 ± 7.4 µM in zebrafish brain (IC50 value of 39.0 ± 1.4 µM). However, the inhibition constant (Ki) was found to be 36.0 ± 0.4 µM with IC50 value of 20.0 ± 1.0 µM, whereas donepezil showed 3.2 ± 0.3 µM with the IC50 value of 0.12 ± 0.04 µM for human acetylcholinesterase. Further, the molecular docking, dynamics and simulation for trans-tephrostachin obtained better binding affinity and efficacy than commercial drugs donepezil and galanthamine. Hence, the isolated compound trans - tephrostachin from T. purpurea shall be further considered for the development of potential drug for the counteraction of Alzheimer's disease progression.
Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Donepezila/farmacologia , Tephrosia/efeitos dos fármacos , Acetilcolinesterase/efeitos dos fármacos , Animais , Bioensaio/métodos , Humanos , Simulação de Acoplamento Molecular/métodos , Extratos Vegetais/farmacologia , Tephrosia/metabolismo , Peixe-ZebraRESUMO
Further investigation of Tephrosia purpurea led to the isolation of a new prenylated flavone, isoglabratephrin B (1) and a new 1,2-ethanedione benzofuran derivative, purpdione B (2). The structures of the new isolates were elucidated on the basis of extensive spectroscopic analysis.