Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity.

Basic Information

ID: ALA4811287

Journal: Bioorg Med Chem Lett

Title: Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity.

Authors: Chen H, Chen X, Sun P, Wu D, Yue H, Pan J, Li X, Zhang C, Wu X, Hua L, Hu W, Yang Z.

Abstract: Inhibiting NLRP3 inflammasome activation is a prospective therapeutic strategy for uncontrolled inflammatory diseases. It is the first time that dronedarone, a multiply ion channel blocker, was identified as a NLRP3-inflammasome inhibitor with an IC₅₀ value of 6.84 μM against IL-1β release. A series of novel 5-amide benzofuran derivatives were designed and synthesized as NLRP3-inflammasome inhibitors. Compound 8c showed slightly increased activity (IC₅₀ = 3.85 μM) against IL-1β release. Notably, treatment with 8c could significantly inhibit NLRP3-mediated IL-1β release and ameliorate peritoneal inflammation in a mouse model of sepsis. Collectively, 8c is a promising lead compound for further chemical development as a NLRP3 inhibitor with anti-inflammation effects.

CiteXplore: 34062252

DOI: 10.1016/j.bmcl.2021.128160

Patent ID: ┄