噻唑-磺胺衍生物的合成、DFT 研究、分子对接和作为潜在阿尔茨海默病抑制剂的生物活性评价。

Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer's Inhibitors.

机构信息

Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.

Department of Chemistry, University of Okara, Okara 56130, Pakistan.

出版信息

Molecules. 2023 Jan 5;28(2):559. doi: 10.3390/molecules28020559.

Alzheimer's disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer's treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer's disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (-) as potent anti-Alzheimer's agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer's potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog was found to have excellent potency (IC = 0.10 ± 0.05 µM for AChE) and (IC = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.

阿尔茨海默病是一种主要的公众脑部疾病，世界卫生组织（WHO）已经揭示出其导致了许多死亡病例。常规的阿尔茨海默病治疗方法，如化疗、手术和放疗，效果并不十分显著，而且通常伴有多种不良反应。因此，有必要寻找一种新的治疗方法，以完全治愈阿尔茨海默病，且没有许多副作用。在这个研究项目中，我们报告了一些新型含噻唑的磺酰胺类似物（-）的合成和生物活性，这些类似物作为有效的抗阿尔茨海默病药物。采用了合适的表征技术，并且采用了密度泛函理论（DFT）计算方法和计算机模拟分子建模，以评估类似物的电子性质和抗阿尔茨海默病的潜力。所有类似物都表现出不同程度的抑制潜力，但与参比药物多奈哌齐（IC = 0.10 ± 0.05 µM 对 AChE，IC = 0.20 ± 0.050 µM 对 BuChE）相比，类似物显示出了极好的活性（IC = 0.10 ± 0.05 µM 对 AChE，IC = 0.20 ± 0.050 µM 对 BuChE）。建立了构效关系，其主要取决于取代基在苯环上的性质、位置、数量和供电子/吸电子效应。