PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 μM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.
摘要：
阿尔茨海默病(AD)是一种慢性,在老年人中常见的进行性脑退行性疾病。到目前为止,没有有效的治疗方法。由于AD发病机制的复杂性，多靶点定向配体（MTDL）策略已被认为是最有前途的方法。在这里，设计并合成了新型水杨酸-多奈哌齐-卡巴拉汀杂种。生物活性结果表明，5a是可逆和选择性的eqBChE抑制剂（IC50=0.53μM），对接提供了可能的机制。化合物5a还显示出潜在的抗炎作用和显著的神经保护作用。此外，图5a在人工胃肠溶液和血浆中表现出有利的稳定性。最后,5a显示了东pol碱诱导的认知功能障碍的潜在认知改善。因此，5a是抗AD的潜在多功能先导化合物。
