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Design, Synthesis, and Biological Activity of Novel Quinone Derivatives as Potent STAT3 Inhibitors for Psoriasis Treatment
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-16 , DOI: 10.1021/acs.jmedchem.4c01055 Ling Chen 1, 2 , Liuliu Wang 1 , Jinlei Gao 1 , Yuanzhu Xie 2 , Xu Deng 1 , Guang Tian 1 , Mingjian Li 1 , Zhongtai Sui 1 , Cailin Luo 1 , Li Liu 1 , Xinyu Huang 1 , Xinyu Zhu 1 , Shuaiwen Zhu 1 , Zhiyong Luo 2 , Dayou Ma 1 , Suyou Liu 1
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-16 , DOI: 10.1021/acs.jmedchem.4c01055 Ling Chen 1, 2 , Liuliu Wang 1 , Jinlei Gao 1 , Yuanzhu Xie 2 , Xu Deng 1 , Guang Tian 1 , Mingjian Li 1 , Zhongtai Sui 1 , Cailin Luo 1 , Li Liu 1 , Xinyu Huang 1 , Xinyu Zhu 1 , Shuaiwen Zhu 1 , Zhiyong Luo 2 , Dayou Ma 1 , Suyou Liu 1
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Psoriasis, which severely affects the sufferer’s life quality, is a chronic skin disease still lacking satisfactory medication. Recently, signal transducer and activator of transcription 3 (STAT3) was revealed playing an important role in the progression of psoriasis. In this paper, a total of 59 quinone derivatives with various scaffolds were designed, synthesized, and evaluated for antipsoriatic potential as STAT3 inhibitors. Among them, 15e was identified as the most potent antipsoriatic agent and could bind to STAT3; reduce both total and phosphorylated STAT3 levels, inhibit the nuclear translocation of STAT3; and, therefore, inhibit the transcription and expression of the propsoriatic factor IL-17A. In vivo experiments on mice showed that the topical application of 15e was effective in alleviating IMQ-induced psoriasis without noticeable side effects. In all, this research rendered 15e as a promising drug candidate for psoriasis.
中文翻译：
作为有效 STAT3 抑制剂治疗银屑病的新型醌衍生物的设计、合成和生物活性
牛皮癣是一种慢性皮肤病，目前尚缺乏满意的药物治疗，严重影响患者的生活质量。最近，信号转导和转录激活因子 3 (STAT3) 被发现在银屑病的进展中发挥着重要作用。在本文中，总共设计、合成了 59 种具有不同支架的醌衍生物，并评估了其作为 STAT3 抑制剂的抗银屑病潜力。其中， 15e被认为是最有效的抗银屑病药物，并且可以与STAT3结合；降低 STAT3 总水平和磷酸化 STAT3 水平，抑制 STAT3 核转位；因此，抑制牛皮癣因子 IL-17A 的转录和表达。小鼠体内实验表明，局部应用15e可有效缓解 IMQ 诱发的牛皮癣，且没有明显的副作用。总之，这项研究使15e成为一种有前途的牛皮癣候选药物。
更新日期：2024-08-16
中文翻译：
作为有效 STAT3 抑制剂治疗银屑病的新型醌衍生物的设计、合成和生物活性
牛皮癣是一种慢性皮肤病，目前尚缺乏满意的药物治疗，严重影响患者的生活质量。最近，信号转导和转录激活因子 3 (STAT3) 被发现在银屑病的进展中发挥着重要作用。在本文中，总共设计、合成了 59 种具有不同支架的醌衍生物，并评估了其作为 STAT3 抑制剂的抗银屑病潜力。其中， 15e被认为是最有效的抗银屑病药物，并且可以与STAT3结合；降低 STAT3 总水平和磷酸化 STAT3 水平，抑制 STAT3 核转位；因此，抑制牛皮癣因子 IL-17A 的转录和表达。小鼠体内实验表明，局部应用15e可有效缓解 IMQ 诱发的牛皮癣，且没有明显的副作用。总之，这项研究使15e成为一种有前途的牛皮癣候选药物。
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