Department of Chemistry, University of Life Sciences, Lublin, Poland.
J Enzyme Inhib Med Chem. 2013 Aug;28(4):816-23. doi: 10.3109/14756366.2012.688041. Epub 2012 May 28.
In the present study, new (1,3,4-thiadiazol-2-yl)benzene-1,3-diol based compounds have been synthesized and their potential anticholinesterases properties have been investigated using the modified of Ellman's spectrophotometric method. The compounds were obtained by the reaction of hydrazides or thiosemicarbazides with aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s. Their chemical structures were elucidated by IR, (1)H-NMR, (13)C-NMR and EI-MS spectral data and elemental analyses. Most of the compounds acted as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors in vitro, with IC₅₀ values ranging from >500 to 0.053 μM and from >500 to 0.105 μM, respectively. The most potent compound 9 (IC₅₀ = 0.053 μM) proved to be selective toward AChE, exhibiting selectivity ratios versus BuChE of ca. 950. The kinetic studies showed that it is a mixed-type of AChE inhibitor. Another compound (2) was active against both enzymes with IC₅₀ values in the low nM range. The structure-activity relationships (SARs) of the compounds under consideration were discussed.
在本研究中，合成了基于新的（1,3,4-噻二唑-2-基）苯-1,3-二醇的化合物，并使用改良的 Ellman 分光光度法研究了它们的潜在抗胆碱酯酶性质。这些化合物是通过酰肼或硫代氨基脲与芳基修饰的亚磺酰基双[(2,4-二羟基苯基)甲硫酮]反应得到的。它们的化学结构通过 IR、(1)H-NMR、(13)C-NMR 和 EI-MS 光谱数据和元素分析进行了阐明。大多数化合物在体外表现出乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制剂的活性，IC₅₀值范围为>500 至 0.053 μM 和>500 至 0.105 μM。最有效的化合物 9（IC₅₀=0.053 μM）对 AChE 具有选择性，对 BuChE 的选择性比值约为 950。动力学研究表明，它是一种混合类型的 AChE 抑制剂。另一种化合物（2）对两种酶均具有活性，IC₅₀值在低 nM 范围内。讨论了所考虑的化合物的结构-活性关系（SARs）。
