Design, synthesis and biological evaluation of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy

摘要

A series of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy were designed, synthesized and biologically evaluated. Among them, compound 71 displayed the most potent inhibitory against COX-2 (IC50 = 0.82 mu M) and antiproliferative activities against Hela cells (IC50 = 0.34 mu M) compared with Celecoxib (IC50 = 0.38 and 7.91 mu M). The further mechanistic studies revealed that 71 could induce apoptosis of Hela cells by mitochondrial depolarization and the antiproliferative activities of 71 were positively correlated with the levels of intracellular NO release in Hela cells. Most notably, 71 could dramatically suppress tumor growth in Hela cells xenografted mouse model. In summary, compound 71 may be promising candidates for cancer therapy. (C) 2018 Elsevier Masson SAS. All rights reserved.