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

Abstract

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 7l displayed the most potent inhibitory against COX-2 (IC₅₀ = 0.82 μM) and antiproliferative activities against Hela cells (IC₅₀ = 0.34 μM) compared with Celecoxib (IC₅₀ = 0.38 and 7.91 μM). The further mechanistic studies revealed that 7l could induce apoptosis of Hela cells by mitochondrial depolarization and the antiproliferative activities of 7l were positively correlated with the levels of intracellular NO release in Hela cells. Most notably, 7l could dramatically suppress tumor growth in Hela cells xenografted mouse model. In summary, compound 7l may be promising candidates for cancer therapy.

Keywords: Anticancer; COX-2 inhibitor; Ferrocene; NO-Releasing; Pyrazole.