Mou Yi, Wen Shuai, Wang Yan, Zhao Yao, Li Ying-Ping, Sha Hong-Kai, Gui Li-Juan, Jiang Zheng-Yu, Xu Xiang-Ming
College of Pharmacy and Chemistry & Chemical Engineering, Taizhou University, Taizhou 225300, China.
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Antioxidants (Basel). 2025 Mar 8;14(3):325. doi: 10.3390/antiox14030325.
The treatment of ulcerative colitis (UC) has been a major medical challenge due to the lack of safe and effective drugs. Molecular hybridization is a promising strategy for the development of drugs with pleiotropic activity, which has been demonstrated in a wide range of diseases. Tofacitinib has exhibited significant effects on the remission of UC, but a series of adverse effects have occurred during its clinical application. Herein, we propose to utilize a molecular hybridization strategy to link tofacitinib with a cytoprotective HS donor (ADTOH) to obtain a series of hybridized molecules ~. Among them, exhibited the best performance in the HS release rate and the cytoprotective effects against dextran sulfate sodium (DSS)-induced injury. The in vivo studies showed that could effectively alleviate DSS-induced colitis by enhancing oxidative stress defense and reducing the inflammatory response, demonstrating that it is more potent than the parent drugs. The data from the present study support that this molecular hybridization strategy provides a promising avenue for the treatment of UC.
由于缺乏安全有效的药物，溃疡性结肠炎（UC）的治疗一直是一项重大的医学挑战。分子杂交是开发具有多效活性药物的一种有前景的策略，这已在多种疾病中得到证实。托法替布已显示出对UC缓解有显著效果，但在其临床应用过程中出现了一系列不良反应。在此，我们提议利用分子杂交策略将托法替布与具有细胞保护作用的硫化氢（HS）供体（ADTOH）连接，以获得一系列杂交分子~。其中， 在HS释放速率和对硫酸葡聚糖钠（DSS）诱导损伤的细胞保护作用方面表现最佳。体内研究表明， 可通过增强氧化应激防御和减轻炎症反应有效缓解DSS诱导的结肠炎，表明它比母体药物更有效。本研究的数据支持这种分子杂交策略为UC治疗提供了一条有前景的途径。
