AbstractBackgroundAcetylcholinesterase (AChE) is one of the most promising targets for treatment of Alzheimer’s disease. The 1,2,3,4‐tetrahydrocarbazole compounds have been reported to inhibit AChE, reduce plaque formation in AD. Hence our focus is on the synthesis and biological assesment of 1,2,3,4‐tetrahydrocarbazole derivative to manage Alzheimer’s disease.MethodA total of 16, 1,2,3,4‐tetrahydrocarbazole derivatives were synthesized and assesed for AChE and BuChE (butyrylcholinesterase) inhibitory effect. After that, the protein‐ligand interactions and pharmacokinetic of most active derivatives were determined using in silico approaches.ResultThe in vitro assays showed that all 1,2,3,4‐tetrahydrocarbazole derivatives inhibited AChE and BuChE. Additionally, the in silico investigations exhibited that the designed derivatives have capability to intearct with both PAS (peripheral anionic) and CAS (catalytic active) sites of chomiesterase enzyme. The pharmacokinetic parameters prediction disclosed that all synthesized compounds have drug like properties.ConclusionThe study revealed that the newly synthesized 1,2,3,4‐tetrahydrocarbazole ligands could be developed as cognitive enhancers and may be employed in cognitive disorders including Alzheimer’s disease. Thus, 1,2,3,4‐tetrahydrocarbazoles might be taken as lead for the management of Alzheimer’s disease.

中文翻译：

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开发 1,2,3,4-四氢咔唑衍生物作为双重结合胆碱酯酶抑制剂

摘要背景乙酰胆碱酯酶（AChE）是治疗阿尔茨海默病最有希望的靶点之一。据报道，1,2,3,4-四氢咔唑化合物可抑制 AChE，减少 AD 斑块形成​​。因此，我们的重点是用于治疗阿尔茨海默病的 1,2,3,4-四氢咔唑衍生物的合成和生物评估。方法总共合成了 16,1,2,3,4-四氢咔唑衍生物并评估了 AChE 和 BuChE（丁酰胆碱酯酶）的抑制作用。之后，使用以下方法确定了大多数活性衍生物的蛋白质-配体相互作用和药代动力学：计算机模拟接近。结果这体外测定表明所有 1,2,3,4-四氢咔唑衍生物均抑制 AChE 和 BuChE。此外，计算机模拟研究表明，设计的衍生物能够与乔米酯酶的 PAS（外周阴离子）和 CAS（催化活性）位点相互作用。药代动力学参数预测表明所有合成的化合物都具有药物样特性。结论研究表明，新合成的1,2,3,4-四氢咔唑配体可以开发为认知增强剂，并可用于治疗包括阿尔茨海默氏病在内的认知障碍。因此，1,2,3,4-四氢咔唑可作为治疗阿尔茨海默病的药物。