新型PDE4抑制剂治疗压疮的设计、合成和生物学评价

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-05-27 DOI:10.1021/acs.jmedchem.5c00505

Xudong Qian,Gang Li,Yan Geng,Jiaxin Chen,Jiayu Li,Yanghui Ou,Jun Wang,Wei Pan,Dengqin He,Lang Xu,Yuanhui Liu,Yali Zhang,Mengjie Li,Dandan Chen,Ligui Chen,Wen-Hua Chen,Hongliang Yao

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引用次数: 0

摘要

压疮（PU）是一种炎症性皮肤病，可引起局部组织溃疡和缺血性坏死。本文设计并合成了一系列新的PDE4抑制剂，用于PU的处理。潜在化合物G1对PDE4D的IC50值为29 nM，抑制TNF-α (IC50 = 13.32 μM)和NO （IC50 = 2.32 μM）的产生。在大鼠PU模型中，G1能够降低皮肤组织中炎症标志物的表达水平，减少表皮层厚度，减少真皮炎症细胞数量，显著增加成纤维细胞数量，有效加快伤口愈合过程。此外，G1在热板试验中通过增加疼痛阈值表现出镇痛作用，这可能在临床中有不同的应用前景。这些结果表明，新的PDE4抑制剂G1是一种有希望的PU治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Design, Synthesis, and Biological Evaluation of New PDE4 Inhibitors for the Treatment of Pressure Ulcers.

Pressure ulcers (PU) are an inflammatory skin disease that causes localized tissue ulceration and ischemic necrosis. In this work, a new series of PDE4 inhibitors were designed and synthesized for the treatment of PU. Potential compound G1 exhibited an IC50 value of 29 nM against PDE4D and inhibited the production of TNF-α (IC50 = 13.32 μM) and NO (IC50 = 2.32 μM). In a rat PU model, G1 exhibited the capability to reduce the expression levels of inflammatory markers in skin tissue, diminish the thickness of the epidermal layer, decrease the number of dermal inflammatory cells, and significantly enhance the quantity of fibroblasts, which effectively expedited the wound healing process. Furthermore, G1 exhibited analgesic effects by increasing the pain threshold under hot plate tests, which may find varying possible applications in the clinic. These results imply that the new PDE4 inhibitor G1 is a promising therapeutic option for PU.

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.