Discovery of Guanidine Derivatives from Buthus martensii Karsch with Metal-Binding and Cholinesterase Inhibition Properties

Molecules

Li-Ning Wang¹  Jing-Jing Fan²  Yu-Ming Liu² 

[1] College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;Department of Pharmacy Engineering, Tianjin University of Technology, Tianjin 300384, China;

关键词: Buthus martensii Karsch;    cholinesterase inhibitor;    guanidine-type alkaloid;    metal-binding;    molecular docking;    Alzheimer’s disease (AD);   

DOI  :  10.3390/molecules26216737

来源: DOAJ

【 摘 要 】

Two rare guanidine-type alkaloids, Buthutin A (1) and Buthutin B (2), along with two other compounds (3, 4), were isolated from Buthus martensii Karsch, and determined using extensive spectroscopic data analysis and high resolution-mass spectrometry. Compound 1 showed the most potent inhibition on AChE and BChE with IC₅₀ values of 7.83 ± 0.06 and 47.44 ± 0.95 μM, respectively. Kinetic characterization of compound 1 confirmed a mixed-type of AChE inhibition mechanism in accordance with the docking results, which shows its interaction with both catalytic active (CAS) and peripheral anionic (PAS) sites. The specific binding of compound 1 to PAS domain of AChE was also confirmed experimentally. Moreover, compounds 1 and 3 exhibited satisfactory biometal binding abilities toward Cu²⁺, Fe²⁺, Zn²⁺ and Al³⁺ ions. These results provide a new evidence for further development and utilization of B. martensii in health and pharmaceutical products.

【 授权许可】

Unknown