Novel synthetic coumarins that targets NF-κB in Hepatocellular carcinoma

摘要: Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor worldwide, and third cause of cancer related death. Constitutive activation NF-κB underlying mechanism behind tumorigenesis this protein regulates expression genes involved in proliferation, survival, drug resistance, angiogenesis metastasis. The design inhibitors which suppress therefore great therapeutic importance treatment HCC. In study, we investigated effect newly synthesized coumarin derivatives against HCC cells, identified (7-Carbethoxyamino-2-oxo-2H-chromen-4-yl)methylpyrrolidine-1 carbodithioate (CPP) as lead compound. Further, evaluated CPP on DNA binding ability NF-κB, CXCL12-induced cell migration invasion, regulated gene products cells. We found that induced cytotoxicity three cells a time dose dependent manner, suppressed NF-κB. significantly decreased invasion. More evidently, inhibits targeted such cyclin D1, Bcl-2, survivin, MMP12 C-Myc. Furthermore, molecular docking analysis suggested interacts with p50 domain p65 subunit, scoring best among 26 docked study. Thus, are reporting potent inhibitor pro-inflammatory pathway carcinoma.