Evaluation of the Ameliorative Potential of 3,5-bis(2-hydroxyethyl)-1,3,5-thiadiazinane-2-thione against Scopolamine-Induced Alzheimer’s Disease

• Published in: International journal of molecular sciences Vol. 25; no. 16; p. 9104
• Main Authors: Shagufta, Ali, Gowhar, Khan, Adnan, Rasheed, Abdur, Deeba, Farah, Ullah, Rahim, Shahid, Muhammad, Ali, Haleema, Khan, Rasool, Shamezai, Najeebullah, Sharif, Naveed
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.08.2024; MDPI
• Subjects: Acetylcholinesterase - metabolism; Alzheimer Disease - chemically induced; Alzheimer Disease - drug therapy; Alzheimer's disease; Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Cholinesterase Inhibitors - pharmacology; Cholinesterase Inhibitors - therapeutic use; Cognitive ability; Disease Models, Animal; Drug dosages; Enzymes; Free radicals; Light; Male; Maze Learning - drug effects; Memory; Mice; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Rats; Scopolamine; Thiadiazines - pharmacology; Thiadiazines - therapeutic use; Thiones - chemistry; Thiones - pharmacology; Thiones - therapeutic use; Toxicity; acetyl choline esterase; THTT; Alzheimer’s disease; scopolamine
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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-bis(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.