Department of Pharmaceutical Chemistry, Anadolu University, Faculty of Pharmacy, Eskişehir, Turkey.
J Enzyme Inhib Med Chem. 2013 Jun;28(3):509-14. doi: 10.3109/14756366.2011.653355. Epub 2012 Feb 3.
In the present study, some thiazole derivatives were synthesized via the ring closure reaction of 1-[2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetyl]thiosemicarbazide with various phenacyl bromides. The chemical structures of the compounds were elucidated by (1)H NMR, (13)C NMR and mass spectral data and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman's spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. The most potent AChE inhibitor was found as compound 4e (IC(50) = 25.5 ± 2.12 µg/mL) followed by compounds 4i (IC(50) = 38.50 ± 2.12 µg/mL), 4c (IC(50) = 58.42 ± 3.14 µg/mL) and 4g (IC(50) = 68 ± 2.12 µg/mL) when compared with eserine (IC(50) = 0.025 ± 0.01 µg/mL). Effective compounds on AChE exhibited weak inhibition on BuChE (IC(50) > 80 µg/mL). MTT assay indicated that the cytotoxic dose (IC(50) = 71.67 ± 7.63 µg/mL) of compound 4e was higher than its effective dose.
在本研究中，通过 1-[2-(2-氧代苯并[d]噻唑-3(2H)-基)乙酰基]硫代半胱氨酸与各种苯乙酮溴化物的环闭合反应合成了一些噻唑衍生物。通过（1）H NMR、（13）C NMR 和质谱数据以及元素分析确定了化合物的化学结构。通过埃伦曼分光光度法的改进，评估了每个衍生物抑制乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的能力。还通过 MTT 测定法研究了化合物的细胞毒性特性。最有效的 AChE 抑制剂是化合物 4e（IC（50）= 25.5 ± 2.12 µg/mL），其次是化合物 4i（IC（50）= 38.50 ± 2.12 µg/mL）、4c（IC（50）= 58.42 ± 3.14 µg/mL）和 4g（IC（50）= 68 ± 2.12 µg/mL），与依色林（IC（50）= 0.025 ± 0.01 µg/mL）相比。对 AChE 有活性的化合物对 BuChE 的抑制作用较弱（IC（50）> 80 µg/mL）。MTT 测定表明，化合物 4e 的细胞毒性剂量（IC（50）= 71.67 ± 7.63 µg/mL）高于其有效剂量。
