Iqbal Tahir, Mubaraki Murad A, Khushal Ahmad, Arif Amena, Fozia Fozia, Shah Shahid Ali, Ahmad Ijaz, Khan Rasool, Rehman Najeeb Ur, Ziaullah Ziaullah
Department of Chemistry, Kohat University of Science and Technology, Kohat, 26000, Pakistan.
Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia.
ChemistryOpen. 2025 Sep;14(9):e202500083. doi: 10.1002/open.202500083. Epub 2025 Jun 17.
Oxidative stress is a major contributor to neurodegenerative diseases, triggering inflammation that ultimately leads to nerve cell death. This study aims to synthesize and characterize 2-(5-cyclopropyl-6-thioxo-1,3,5-thiadiazinan-3-yl) acetic acid COX-2 and scrutinize the neuroprotective efficacy in a pentylenetetrazole-induced mice model of epilepsy in a mice model. The compound is synthesized via microwave-assisted method and characterized by infrared, nuclear magnetic resonance, and electron ionization mass Spectroscopy. The vivo experiments involve behavioral assessments (Morris water maze and Y-maze tests) and biochemical analyses (antioxidant enzymes and inflammatory markers). Treatment with the synthesized compound significantly restores antioxidant enzyme levels (catalase, peroxidase peroxidation, superoxide dismutase, and glutathione), reduces lipid peroxidation, improves cognitive performance, and suppresses the expression of inflammatory proteins (p-JNK, TNF-α, and COX-2). These findings suggest that 2-(5-cyclopropyl-6-thioxo-1,3,5-thiadiazinan-3-yl) acetic acid possesses strong antioxidant, anti-inflammatory, and neuroprotective properties, making it a promising candidate for the treatment of oxidative stress-related neurodegenerative disorders.
氧化应激是神经退行性疾病的主要促成因素,引发炎症,最终导致神经细胞死亡。本研究旨在合成并表征2-(5-环丙基-6-硫代-1,3,5-噻二嗪-3-基)乙酸COX-2,并在戊四氮诱导的小鼠癫痫模型中仔细研究其神经保护功效。该化合物通过微波辅助方法合成,并通过红外光谱、核磁共振和电子电离质谱进行表征。体内实验包括行为评估(莫里斯水迷宫和Y迷宫测试)和生化分析(抗氧化酶和炎症标志物)。用合成化合物进行治疗可显著恢复抗氧化酶水平(过氧化氢酶、过氧化物酶过氧化、超氧化物歧化酶和谷胱甘肽),减少脂质过氧化,改善认知表现,并抑制炎症蛋白(p-JNK、TNF-α和COX-2)的表达。这些发现表明,2-(5-环丙基-6-硫代-1,3,5-噻二嗪-3-基)乙酸具有强大的抗氧化、抗炎和神经保护特性,使其成为治疗氧化应激相关神经退行性疾病的有前途的候选药物。