{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:31Z","timestamp":1760145631508,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s 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\u2019s 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\u2019s 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 \u00b5g\/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 \u00b5g\/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\u2019s model. The test compound may be beneficial, subject to further elaborate investigation for anti-amyloid disease-modifying properties in AD.<\/jats:p>","DOI":"10.3390\/ijms25169104","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T05:16:24Z","timestamp":1724649384000},"page":"9104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of the Ameliorative Potential of 3,5-bis(2-hydroxyethyl)-1,3,5-thiadiazinane-2-thione against Scopolamine-Induced Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"family":"Shagufta","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9749-0645","authenticated-orcid":false,"given":"Gowhar","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-2983","authenticated-orcid":false,"given":"Adnan","family":"Khan","sequence":"additional","affiliation":[{"name":"DHQ Teaching Hospital Timergara, Lower Dir, Khyber Pakhtunkhwa (KPK), Timergara 18300, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdur","family":"Rasheed","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farah","family":"Deeba","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahim","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar 25000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6953-7848","authenticated-orcid":false,"given":"Muhammad","family":"Shahid","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, CECOS University of IT and Emerging Sciences, Peshawar 25000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haleema","family":"Ali","sequence":"additional","affiliation":[{"name":"Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasool","family":"Khan","sequence":"additional","affiliation":[{"name":"Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najeebullah","family":"Shamezai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveed","family":"Sharif","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Diagnostic Medicine, Khyber Medical University Peshawar, Khyber Pakhtunkhwa (KPK), Peshawar 25100, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ayaz, M., Junaid, M., Ullah, F., Subhan, F., Sadiq, A., Ali, G., Ovais, M., Shahid, M., Ahmad, A., and Wadood, A. (2017). Anti-Alzheimer\u2019s studies on \u03b2-sitosterol isolated from Polygonum hydropiper L.. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00697"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s13596-017-0268-8","article-title":"Memory enhancing activity of Lawsonia inermis Linn. leaves against scopolamine induced memory impairment in Swiss albino mice","volume":"17","author":"Rajesh","year":"2017","journal-title":"Orient. Pharm. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jalz.2007.04.381","article-title":"Forecasting the global burden of Alzheimer\u2019s disease","volume":"3","author":"Brookmeyer","year":"2007","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.4314\/tjpr.v17i8.11","article-title":"Lavandula stoechas L. alleviates dementia by preventing oxidative damage of cholinergic neurons in mice brain","volume":"17","author":"Mushtaq","year":"2018","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2017.09.043","article-title":"The present and future of pharmacotherapy of Alzheimer\u2019s disease: A comprehensive review","volume":"815","author":"Anand","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kametani, F., and Hasegawa, M. (2018). Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer\u2019s disease. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00025"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/BF00471738","article-title":"Synthesis and properties of functional derivatives of 1,3,4-thiadiazines and condensed systems based on these compounds","volume":"27","author":"Novikova","year":"1991","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_8","first-page":"244","article-title":"Tetrahydro-2H-1, 3,5-thiadiazine-5-(4-pyridylcarboxamide)-2-thione derivatives as prodrugs for isoniazid; synthesis, investigations and in vitro antituberculous activity","volume":"54","author":"Hassanin","year":"1999","journal-title":"Pharmazie"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2174\/1874104501105010051","article-title":"Thiadiazine derivatives as antiprotozoal new drugs","volume":"5","author":"Bermello","year":"2011","journal-title":"Open Med. Chem. J."},{"key":"ref_10","first-page":"160","article-title":"Syntheses and antifungal activities of some 3-(2-phenylethyl)-5-substituted-tetrahydro-2H-1, 3,5-thiadiazine-2-thiones","volume":"42","author":"Ertan","year":"1992","journal-title":"Arzneim. Forsch."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrd2896","article-title":"Alzheimer\u2019s disease: Strategies for disease modification","volume":"9","author":"Citron","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.31661\/gmj.v6i3.820","article-title":"Drugs Induced Alzheimer\u2019s Disease in Animal Model","volume":"6","author":"Malekzadeh","year":"2017","journal-title":"Galen Med. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Balaban, H., Nazirolu, M., Demirci, K., and \u00d6vey, \u0130.S. (2017). The protective role of selenium on scopolamine-induced memory impairment, oxidative stress, and apoptosis in aged rats: The involvement of TRPM2 and TRPV1 channels. Mol. Neurobiol., 54.","DOI":"10.1007\/s12035-016-9835-0"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"703","DOI":"10.2174\/1389557520666200103100521","article-title":"Potent acetylcholinesterase inhibitors: Potential drugs for Alzheimer\u2019s disease","volume":"20","year":"2020","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bbr.2007.05.016","article-title":"The point of entry contributes to the organization of exploratory behavior of rats on an open field: An example of spontaneous episodic memory","volume":"182","author":"Nemati","year":"2007","journal-title":"Behav. Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0091-3057(00)00386-5","article-title":"Effects of prenatal AZT+ 3TC treatment on open field behavior and responsiveness to scopolamine in adult mice","volume":"67","author":"Calamandrei","year":"2000","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"012","DOI":"10.7324\/JAPS.2015.50203","article-title":"In-vitro Screening for acetylcholinesterase enzyme inhibition potential and antioxidant activity of extracts of Ipomoea aquatica Forsk: Therapeutic lead for Alzheimer\u2019s disease","volume":"5","author":"Dhanasekaran","year":"2015","journal-title":"J. Appl. Pharm. Sci"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40659-015-0011-1","article-title":"Anticholinesterse and antioxidant investigations of crude extracts, subsequent fractions, saponins and flavonoids of Atriplex laciniata L.: Potential effectiveness in Alzheimer\u2019s and other neurological disorders","volume":"48","author":"Kamal","year":"2015","journal-title":"Biol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40659-015-0010-2","article-title":"Antioxidant and anticholinesterase investigations of Rumex hastatus D. Don: Potential effectiveness in oxidative stress and neurological disorders","volume":"48","author":"Ahmad","year":"2015","journal-title":"Biol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ejphar.2017.08.040","article-title":"Gabapentin and its salicylaldehyde derivative alleviate allodynia and hypoalgesia in a cisplatin-induced neuropathic pain model","volume":"814","author":"Ahmad","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rukh, L., Ali, G., Ullah, R., Islam, N.U., and Shahid, M. (2020). Efficacy assessment of salicylidene salicylhydrazide in chemotherapy associated peripheral neuropathy. Eur. J. Pharmacol., 173481.","DOI":"10.1016\/j.ejphar.2020.173481"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108083","DOI":"10.1016\/j.intimp.2021.108083","article-title":"Attenuation of spatial memory in 5xFAD mice by targeting cholinesterases, oxidative stress and inflammatory signaling using 2-(hydroxyl-(2-nitrophenyl)methyl)cyclopentanone","volume":"100","author":"Ullah","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ullah, R., Ali, G., Khan, A., Ahmad, S., and Al-Harrasi, A. (2021). Cyclopentanone Derivative Attenuates Memory Impairment by Inhibiting Amyloid Plaques Formation in the 5xFAD Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179559"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biopha.2017.10.088","article-title":"Ameliorating effect of Alpinia oxyphylla\u2014Schisandra chinensis herb pair on cognitive impairment in a mouse model of Alzheimer\u2019s disease","volume":"97","author":"Wang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"108970","DOI":"10.1016\/j.intimp.2022.108970","article-title":"Tannic acid inhibits lipopolysaccharide-induced cognitive impairment in adult mice by targeting multiple pathological features","volume":"110","author":"Ullah","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.cbi.2017.11.008","article-title":"20 (S)-protopanaxadiol (PPD) alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of Egr-1, c-Fos and c-Jun in mice","volume":"279","author":"Lu","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.brainres.2016.05.017","article-title":"\u03b2-glucan attenuated scopolamine induced cognitive impairment via hippocampal acetylcholinesterase inhibition in rats","volume":"1644","author":"Haider","year":"2016","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108674","DOI":"10.1016\/j.intimp.2022.108674","article-title":"The 7-Hydroxyflavone attenuates chemotherapy-induced neuropathic pain by targeting inflammatory pathway","volume":"107","author":"Ullah","year":"2022","journal-title":"Int. Immunopharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/9104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:41:05Z","timestamp":1760110865000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/9104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":28,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25169104"],"URL":"https:\/\/doi.org\/10.3390\/ijms25169104","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,8,22]]}}}