Details

Autor(en) / Beteiligte

• Gu, Chenming
• Liu, Jiayuan
• Qian, Fei
• Yu, Wenchao
• Huang, Doudou
• Shen, Jingshan
• Feng, Chenguo
• Chen, Kaixian
• Li, Yiming
• Jiang, Xiangrui
• Xu, Yechun
• Zhang, Liuqiang

Titel

Identification of Dihydrobenzofuran Neolignans as Novel PDE4 Inhibitors and Evaluation of Antiatopic Dermatitis Efficacy in DNCB-Induced Mice Model

Ist Teil von

• Journal of medicinal chemistry, 2024-03, Vol.67 (6), p.4855-4869

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3′,4-O-dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from Magnolia biondii with moderate potency against PDE4 (IC50 = 3.26 ± 0.28 μM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of 7b-1 that showed high inhibitory potency on PDE4 (IC50 = 0.17 ± 0.02 μM), good anti-TNF-α activity (EC50 = 0.19 ± 0.10 μM), remarkable selectivity profile, and good skin permeability. The topical treatment of 7b-1 resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.