The discovery of acetylcholinesterase inhibitors is important for the treatment of Alzheimer’s disease (AD), known as the most common type of dementia. Due to the side effects of commonly used acetylcholinesterase inhibitors, studies for the detection of new inhibitors are increasing day by day. In this study, we investigated the effects of some sulfonamide derivatives (S1–S4 and S1i–S4i) on AChE enzymes. The best pose of the active compounds to understand the mechanism of possible inhibition in interaction of enzyme-sulfonamide derivative were performed docking studies after in vitro experimental results. ADME-related physicochemical and pharmacokinetic properties of the synthesized 4-aminobenzenesulfonamide derivatives were the compatibility with Lipinski’s rule of five. We found that the synthesized derivatives of sulfonamides show potential inhibitor properties for AChE with K_i constants in the range of 2.54 ± 0.22–299.60 ± 8.73 µM. The derivatives of sulfonamides exhibited different inhibition type. We determined that the derivatives (S1, S1i, S3, and S3i) showed a competitive inhibition effect, whereas others (S2, S2i, S4, and S4i) showed mixed-type inhibition. As a result, the sulfonamide derivatives can be used as an alternative acetylcholinesterase inhibitor due to this effect. Inhibitors with fewer side effects, are thought to be important in the treatment of AD.

中文翻译：

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作为有效的AChE抑制剂的4-（苄基亚氨基）-和4-（苄基氨基）-苯磺酰胺衍生物的分子对接和研究

乙酰胆碱酯酶抑制剂的发现对于阿尔茨海默氏病（AD）（一种最常见的痴呆类型）的治疗非常重要。由于常用的乙酰胆碱酯酶抑制剂的副作用，检测新抑制剂的研究日益增加。在这项研究中，我们研究了某些磺酰胺衍生物（S1-S4和S1i-S4i）对AChE酶的影响。在体外实验结果之后，进行了对接研究，以了解活性化合物了解酶-磺酰胺衍生物相互作用的可能抑制机制的最佳姿势。合成的4-氨基苯磺酰胺衍生物与ADME有关的理化和药代动力学特性与Lipinski的5法则相容。K _i常数在2.54±0.22–299.60±8.73 µM的范围内。磺酰胺衍生物表现出不同的抑制类型。我们确定衍生物（S1，S1i，S3和S3i）表现出竞争抑制作用，而其他衍生物（S2，S2i，S4和S4i）表现出混合抑制作用。结果，由于这种作用，磺酰胺衍生物可用作替代的乙酰胆碱酯酶抑制剂。副作用少的抑制剂被认为对AD的治疗很重要。