噻唑类似物作为阿尔茨海默病新抑制剂的合成、分子对接、乙酰胆碱酯酶和丁酰胆碱酯酶抑制潜力
Synthesis, molecular docking, acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease.
作者信息
Rahim Fazal, Javed Muhammad Tariq, Ullah Hayat, Wadood Abdul, Taha Muhammad, Ashraf Muhammad, Khan Muhammad Anas, Khan Fahad, Mirza Salma, Khan Khalid M
机构信息
Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan.
Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan.
出版信息
Bioorg Chem. 2015 Oct;62:106-16. doi: 10.1016/j.bioorg.2015.08.002. Epub 2015 Aug 19.
A series of thirty (30) thiazole analogs were prepared, characterized by (1)H NMR, (13)C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC50 value ranging between 1.59±0.01 and 389.25±1.75μM when compared with the standard eserine (IC50, 0.85±0.0001μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC50 values 1.59±0.01, 1.77±0.01, 6.21±0.01, 7.56±0.01, 8.46±0.01, 14.81±0.32 and 16.54±0.21μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3±0.50, 35.3±0.64, 36.6±0.70, 44.81±0.81, 46.36±0.84, 48.2±0.06 and 48.72±0.91μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking.
制备了一系列30种噻唑类似物，通过¹H NMR、¹³C NMR和EI-MS对其进行表征，并评估了它们对乙酰胆碱酯酶和丁酰胆碱酯酶的抑制潜力。与标准毒扁豆碱（IC50，0.85±0.0001μM）相比，所有类似物均表现出不同程度的丁酰胆碱酯酶抑制活性，IC50值在1.59±0.01至389.25±1.75μM之间。IC50值分别为1.59±0.01、1.77±0.01、6.21±0.01、7.56±0.01、8.46±0.01、14.81±0.32和16.54±0.21μM的类似物15、7、12、9、14、1、30表现出优异的抑制潜力。七种类似物15、20、19、24、28、30和25表现出良好的乙酰胆碱酯酶抑制潜力，IC50值分别为21.3±0.50、35.3±0.64、36.6±0.70、44.81±0.81、46.36±0.84、48.2±0.06和48.72±0.91μM。所有其他类似物也表现出良好至中等程度的酶抑制作用。通过分子对接确定了这些化合物的结合模式。
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