Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan.
DHQ Teaching Hospital Timergara, Lower Dir, Khyber Pakhtunkhwa (KPK), Timergara 18300, Pakistan.
Int J Mol Sci. 2024 Aug 22;25(16):9104. doi: 10.3390/ijms25169104.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, marked by cognitive impairment. Currently, the available treatment provides only symptomatic relief and there is a great need to design and formulate new drugs to stabilize AD. In the search for a new anti-Alzheimer's drug, 3,5-(2-hydroxyethyl)-1,3,5-thiadiazinane-2-thione (THTT), a tetrahydro-2H-1,3,5-thiadiazine-2-thione derivative, was investigated against a scopolamine-induced Alzheimer's model. The selected test compound was administered intraperitoneally in three doses (15 mg/kg, 30 mg/kg, and 45 mg/kg). The test compound exhibited an IC50 value of 69.41 µg/mL, indicating its ability to inhibit the acetylcholinesterase enzyme. An antioxidant DPPH assay revealed that the IC50 value of the test compound was 97.75 µg/mL, which shows that the test compound possesses antioxidant activity. The results of behavior tests including the Y-maze and elevated plus maze (EPM) show that the test compound improved short-term memory and spatial memory, respectively. Furthermore, in the Morris water maze (MWM) and light/dark model, the test compound shows improvements in learning and memory. Moreover, the results of histological studies show that the test compound can protect the brain against the harmful effects of scopolamine. Overall, the findings of our investigation suggest that our chosen test compound has disease-modifying and neuroprotective activities against the scopolamine-induced Alzheimer's model. The test compound may be beneficial, subject to further elaborate investigation for anti-amyloid disease-modifying properties in AD.
阿尔茨海默病(AD)是最常见的神经退行性疾病,其特征是认知障碍。目前,可用的治疗方法仅提供症状缓解,因此非常需要设计和制定新的药物来稳定 AD。在寻找新的抗阿尔茨海默病药物时,研究了噻唑烷-2-硫酮(THTT),一种四氢-2H-1,3,5-噻嗪-2-硫酮衍生物,以对抗东莨菪碱诱导的 AD 模型。选择的测试化合物以三种剂量(15mg/kg、30mg/kg 和 45mg/kg)腹腔给药。测试化合物的 IC50 值为 69.41µg/mL,表明其抑制乙酰胆碱酯酶的能力。抗氧化 DPPH 测定表明,测试化合物的 IC50 值为 97.75µg/mL,表明测试化合物具有抗氧化活性。包括 Y 迷宫和高架十字迷宫(EPM)在内的行为测试的结果表明,测试化合物分别改善了短期记忆和空间记忆。此外,在 Morris 水迷宫(MWM)和明暗模型中,测试化合物显示出学习和记忆的改善。此外,组织学研究的结果表明,测试化合物可以保护大脑免受东莨菪碱的有害影响。总体而言,我们的研究结果表明,我们选择的测试化合物具有针对东莨菪碱诱导的 AD 模型的疾病修饰和神经保护活性。该测试化合物可能有益,但其抗淀粉样变性疾病修饰特性需要进一步详细研究。