Synthesis and identification of quinoline derivatives as topoisomerase I inhibitors with potent antipsoriasis activity in an animal model.
Bioorganic chemistry(2019)
摘要
Psoriasis is a chronic inflammatory and immune-mediated skin disease. Although certain agents have shown clinical success in treating psoriasis, development of safe and effective strategies for the treatment of this condition remains important. Research suggests that DNA topoisomerase I (Topo I) inhibitors may have potent psoriasis-ameliorating effects. Here, 25 quinoline derivatives were synthesized and identified as Topo I inhibitors. These compounds inhibited the 12-O-tetradecanoylphorbol-13-acetate-induced mouse ear inflammation. The most potent analogs, 5i and 5l, suppressed the expression of inflammatory cytokines in lipopolysaccharide-stimulated HaCaT cells. Additionally, the lead compounds significantly improved imiquimod-induced psoriasis-like inflammation in mice. Moreover, the expression levels of cytokines and inflammatory mediators, such as interleukin (IL)-17A, IL-22, IL-23, nuclear factor-κB subunit p65, tumor necrosis factor-α, and interferon-γ, were dramatically inhibited in the dorsal skin of 5i- and 5l-treated mice. These findings indicate that the inhibition of Topo I activity may potentially be an effective strategy for psoriasis treatment.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要