Rahim Fazal, Javed Muhammad Tariq, Ullah Hayat, Wadood Abdul, Taha Muhammad, Ashraf Muhammad, Khan Muhammad Anas, Khan Fahad, Mirza Salma, Khan Khalid M
Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan.
Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan.
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。
