1H nuclear magnetic resonance relaxation investigation of huperzine E binding to acetylcholinesterase

Abstract

In order to search for better acetylcholinesterase (AchE) inhibitors, the binding properties of AchE with huperizine E, which is a derivative of huperzine A, were investigated with 1 H nuclear magnetic resonance ( 1 H NMR) method. The nonselective, selective and double-selective spin-lattice relaxation rates of some protons in huperzine E were acquired in the absence and presence of AchE at a concentration ratio of [ligand]/[protein] = 1 : 0.005. The enhancements of selective relaxation rates of these protons were obvious after adding AchE. The molecular motional correlation times of two pairs of protons, H-1a/H-1b and H-2/H-3, in the bound state at T = 298 K were 11.7 and 9.46 ns respectively, while they were 27.7 and 35.2 ps in the free state. All of these show that huperzine E has high binding affinity with AchE.

Detection by UPLC/ESI-TOF-MS of Alkaloids in Three Lycopodiaceae Species from French Polynesia and Their Anticholinesterase Activity

“…We first noted the presence of lycopodine and lycodoline in all three studied clubmosses, whatever the harvesting season, in relatively stable and high quantities. The presence of lycopodine is all the more interesting because of its reported beneficial medicinal properties, such as anticholinesterase activity [12,13]. Traces of huperzine A were detected only in L. cernua.…”

“…Among the different alkaloids identified, three of them are volatile, lycodine, lycopodine and lycodoline [10]. Five are known for having acetylcholinesterase inhibitor activity, huperzine A, huperzine B [11], huperzine E [12], lycopodine [13,14], and huperzinine [15]. Two compounds, cernuine and lycocernuine, have been isolated previously from L. cernua [16], and lycopladine B is known for having no in vitro cytotoxicity against murine lymphoma L1210 cells and human epidermoid carcinoma KB cells [17].…”