PDF(Pubmed)
Abstract：
Lignan phytomolecules demonstrate promising anti-Alzheimer activity by alleviating dementia and preserving nerve cells. The purpose of this work is to characterize the lignans of Anisacanthus virgularis and explore their potential anti-acetylcholinesterase and anti-ageing effects. Phytochemical investigation of A. virgularis aerial parts afforded a new furofuranoid-type lignan (1), four known structural analogues, namely pinoresinol (2), epipinoresinol (3), phillyrin (4), and pinoresinol 4-O-β-d-glucoside (5), in addition to p-methoxy-trans-methyl cinnamate (6) and 1H-indole-3-carboxaldehyde (7). The structures were established from thorough spectroscopic analyses and comparisons with the literature. Assessment of the anticholinesterase activity of the lignans 1-5 displayed noticeable enzyme inhibition of 1 (IC50 = 85.03 ± 4.26 nM) and 5 (64.47 ± 2.75 nM) but lower activity of compounds 2-4 as compared to the reference drug donepezil. These findings were further emphasized by molecular docking of 1 and 5 with acetylcholinesterase (AChE). Rapid overlay chemical similarity (ROCS) and structure-activity relationships (SAR) analysis highlighted and rationalized the anti-AD capability of these compounds. Telomerase activation testing of the same isolates revealed 1.64-, 1.66-, and 1.72-fold activations in cells treated with compounds 1, 5, and 4, respectively, compared to untreated cells. Our findings may pave the way for further investigations into the development of anti-Alzheimer and/or anti-ageing drugs from furofuranoid-type lignans.
摘要：
木质素植物分子通过减轻痴呆和保留神经细胞而显示出有希望的抗阿尔茨海默病活性。这项工作的目的是表征虎尾草的木脂素，并探索其潜在的抗乙酰胆碱酯酶和抗衰老作用。对A.virgularis地上部分的植物化学研究提供了一种新的呋喃类木酚素（1），四种已知的结构类似物，即松脂醇(2)，表松醇（3），连翘苷（4），和松脂醇4-O-β-d-葡萄糖苷(5)，除了对甲氧基-反式-甲基肉桂酸酯(6)和1H-吲哚-3-甲醛(7)。通过彻底的光谱分析和与文献的比较来建立结构。木脂素1-5的抗胆碱酯酶活性的评估显示出明显的酶抑制1(IC50=85.03±4.26nM)和5(64.47±2.75nM),但与参考药物多奈哌齐相比,化合物2-4的活性较低。1和5与乙酰胆碱酯酶（AChE）的分子对接进一步强调了这些发现。快速叠加化学相似性（ROCS）和结构-活性关系（SAR）分析突出并合理化了这些化合物的抗AD能力。相同分离株的端粒酶激活测试显示1.64-，1.66-，和分别用化合物1、5和4处理的细胞中的1.72倍激活，与未处理的细胞相比。我们的发现可能为进一步研究从呋喃类木脂素中开发抗阿尔茨海默病和/或抗衰老药物铺平道路。
