Naaz Huma, Singh Swati, Pandey Veda P, Singh Priyanka, Dwivedi Upendra N
Department of Biochemistry, University of Lucknow, India.
Indian J Biochem Biophys. 2013 Apr;50(2):120-5.
Alzheimer's disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms is biochemically characterized by a significant decrease in the brain neurotransmitter acetylcholine (ACh). Plant-derived metabolites, including alkaloids have been reported to possess neuroprotective properties and are considered to be safe, thus have potential for developing effective therapeutic molecules for neurological disorders, such as AD. Therefore, in the present study, thirteen plant-derived alkaloids, namely pleiocarpine, kopsinine, pleiocarpamine (from Pleiocarpa mutica, family: Annonaceae), oliveroline, noroliveroline, liridonine, isooncodine, polyfothine, darienine (from Polyalthia longifolia, family: Apocynaceae) and eburnamine, eburnamonine, eburnamenine and geissoschizol (from Hunteria zeylanica, family: Apocynaceae) were analyzed for their anti-cholinergic action through docking with acetylcholinesterase (AChE) as target. Among the alkaloids, pleiocarpine showed promising anti-cholinergic potential, while its amino derivative showed about six-fold higher anti-cholinergic potential than pleiocarpine. Pleiocarpine and its amino derivative were found to be better inhibitors of AChE, as compared to commonly used drugs tacrine (brand name: Cognex) and rivastigmine (brand name: Exelon), suggesting development of these molecules as potential therapeutics in future.
阿尔茨海默病（AD）是一种具有多种认知和神经精神症状的进行性神经退行性疾病，其生化特征是大脑神经递质乙酰胆碱（ACh）显著减少。据报道，包括生物碱在内的植物衍生代谢产物具有神经保护特性，且被认为是安全的，因此有潜力开发用于治疗神经疾病（如AD）的有效治疗分子。因此，在本研究中，通过以乙酰胆碱酯酶（AChE）为靶点进行对接，分析了13种植物衍生生物碱，即pleiocarpine、kopsinine、pleiocarpamine（来自多脉暗罗，番荔枝科）、oliveroline、去甲oliveroline、liridonine、异诺可定、polyfothine、darienine（来自长叶暗罗，夹竹桃科）以及eburnamine、eburnamonine、eburnamenine和geissoschizol（来自锡兰蕊木，夹竹桃科）的抗胆碱作用。在这些生物碱中，pleiocarpine显示出有前景的抗胆碱潜力，而其氨基衍生物的抗胆碱潜力比pleiocarpine高约六倍。与常用药物他克林（商品名：Cognex）和卡巴拉汀（商品名：Exelon）相比，pleiocarpine及其氨基衍生物被发现是更好的AChE抑制剂，这表明这些分子未来有可能开发成为潜在的治疗药物。
