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 <b>G1</b> exhibited an IC<sub>50</sub> value of 29 nM against PDE4D and inhibited the production of TNF-α (IC<sub>50</sub> = 13.32 μM) and NO (IC<sub>50</sub> = 2.32 μM). In a rat PU model, <b>G1</b> 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, <b>G1</b> 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 <b>G1</b> is a promising therapeutic option for PU.
Authors
- Liang‐Chieh Chen (ORCID: https://orcid.org/0000-0003-4891-3848)
- Wei Pan
- Yanghui Ou (ORCID: https://orcid.org/0000-0001-9481-9882)
- Dengqin He
- Xudong Qian (ORCID: https://orcid.org/0000-0002-6183-256X)
- Jiaxin Chen (ORCID: https://orcid.org/0000-0003-1506-2223)
- Yali Zhang (ORCID: https://orcid.org/0000-0002-9115-5758)
- Dandan Chen (ORCID: https://orcid.org/0000-0003-0918-7337)
- Jiayu Li (ORCID: https://orcid.org/0000-0002-5398-1151)
- Liu Y (ORCID: https://orcid.org/0000-0001-8568-623X)
- Mengjie Li (ORCID: https://orcid.org/0000-0001-8573-7025)
- Wenhua Chen (ORCID: https://orcid.org/0000-0003-3722-123X)
- Xu Lang
- Hongliang Yao (ORCID: https://orcid.org/0000-0002-0795-2878)
- Yan Geng (ORCID: https://orcid.org/0009-0008-2658-7598)
- Jun Wang (ORCID: https://orcid.org/0000-0001-8183-7600)
- Gang Li (ORCID: https://orcid.org/0000-0003-4191-7643)
Institutions
- Guangdong Academy of Sciences (CN)
- Institute of Zoology (CN)
- Wuyi University (CN)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-05-27
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c00505
- Citations
- 2
- Primary Topic
- Phosphodiesterase function and regulation
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Special Project for Research and Development in Key areas of Guangdong Province
- Basic and Applied Basic Research Foundation of Guangdong Province