Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) Raebareli, Lucknow, Uttar Pradesh, India.
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) Raebareli, Lucknow, Uttar Pradesh, India.
Drug Dev Res. 2020 Apr;81(2):165-183. doi: 10.1002/ddr.21587. Epub 2019 Aug 20.
Alzheimer's disease (AD), a complex neurodegenerative disorder causing multiple cellular changes including impaired cholinergic system, beta-amyloid (βA) aggregation, tau hyperphosphorylation, metal dyshomeostasis, neuroinflammation, and many other pathways are involved in the pathogenesis of the disease. However, the exact cause of the disease is not known. Natural products such as flavonoids, alkaloids, resveratrol, and curcumin have multifunctional properties, and have drawn the attention of the researchers because these molecules are capable of interacting concurrently with the multiple targets of AD. Therefore, natural products and their derivatives with proven efficacy could be used in the management of the neurodegenerative disorders. This review focuses on the natural product based multitarget directed ligands like tacrine-coumarin, tacrine-huperzine A, harmine-isoxazoline, berberine-thiophenyl, galantamine-indole, pyridoxine-resveratrol, donepezil-curcumin and their mode of action.
阿尔茨海默病(AD)是一种复杂的神经退行性疾病,导致多种细胞变化,包括胆碱能系统受损、β-淀粉样蛋白(βA)聚集、tau 过度磷酸化、金属动态平衡失调、神经炎症和许多其他途径都涉及疾病的发病机制。然而,该病的确切病因尚不清楚。黄酮类、生物碱、白藜芦醇和姜黄素等天然产物具有多功能特性,引起了研究人员的关注,因为这些分子能够同时与 AD 的多个靶点相互作用。因此,具有明确疗效的天然产物及其衍生物可用于神经退行性疾病的治疗。本综述重点介绍了基于天然产物的多靶点导向配体,如他克林-香豆素、他克林-石杉碱甲、哈尔明-异噁唑啉、小檗碱-噻吩、加兰他敏-吲哚、吡哆醇-白藜芦醇、多奈哌齐-姜黄素及其作用模式。