Ingkaninan Kornkanok, Phengpa Preeda, Yuenyongsawad Supreeya, Khorana Nantaka
Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
J Pharm Pharmacol. 2006 May;58(5):695-700. doi: 10.1211/jpp.58.5.0015.
Acetylcholinesterase (AChE) inhibitors have lately gained interest as potential drugs in the treatment of Alzheimer's disease. Three AChE inhibitors were isolated from tubers of a Thai medicinal plant, Stephania venosa (Bl) Spreng. They were identified as quaternary protoberberine alkaloids, stepharanine, cyclanoline and N-methyl stepholidine. They expressed inhibitory activity on AChE with IC50 values (concentration that caused 50% inhibition of activity) of 14.10 +/- 0.81, 9.23 +/- 3.47 and 31.30 +/- 3.67 microM, respectively. The AChE inhibitory activity of these compounds was compared with those of the related compounds, palmatine, jatrorrhizine and berberine, as well as tertiary protoberberine alkaloids isolated from the same plant, stepholidine and corydalmine. The results suggest that the positive charge at the nitrogen of the tetrahydroisoquinoline portion, steric substitution at the nitrogen, planarity of the molecule or substitutions at C-2, -3, -9, and -10 affect the AChE inhibitory activity of protoberberine alkaloids.
乙酰胆碱酯酶（AChE）抑制剂近来作为治疗阿尔茨海默病的潜在药物受到关注。从泰国药用植物地不容（Stephania venosa (Bl) Spreng.）的块茎中分离出三种AChE抑制剂。它们被鉴定为季铵原小檗碱生物碱，千金藤宁碱、环南藤宁碱和N - 甲基千金藤啶碱。它们对AChE表现出抑制活性，IC50值（导致50%活性抑制的浓度）分别为14.10±0.81、9.23±3.47和31.30±3.67微摩尔。将这些化合物的AChE抑制活性与相关化合物巴马汀、药根碱和小檗碱，以及从同一植物中分离出的叔铵原小檗碱生物碱千金藤啶碱和紫堇胺的活性进行了比较。结果表明，四氢异喹啉部分氮原子上的正电荷、氮原子上的空间取代、分子的平面性或C - 2、- 3、- 9和- 10位上的取代会影响原小檗碱生物碱的AChE抑制活性。
