Zebrafish bio-assay guided isolation of human acetylcholinesterase inhibitory trans-tephrostachin from Tephrosia purpurea (L.) Pers

• Published in: Neuroscience letters 2018-11, Vol.687, p.268-275
• Main Authors: Pitchai, Arjun, Nagarajan, Nagasundaram, Vincent, Samuel Gnana Prakash, Rajaretinam, Rajesh Kannan
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Enzyme kinetics; Molecular docking and dynamics; trans-Tephrostachin; Zebrafish
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2018.09.058

•First report on the isolation of acetylcholinesterase inhibitory trans- tephrostachin from Tephrosia purpurea (L.) Pers.•Enzyme inhibition mechanism favored the mixed type for both zebrafish brain extract and human acetyl cholinesterase.•In silico studies of trans-tephrostachin confirmed the better binding affinity and efficacy than donepezil and galanthamine. 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.