RESUMEN
Targeting tumor stemness is an innovative approach to cancer treatment. Zinc Finger Protein 207 (ZNF207) is a promising target for weakening the stemness of glioma cells. Here, a series of novel N-(anthracen-9-ylmethyl) benzamide derivatives against ZNF207 were rationally designed and synthesized. The inhibitory activity was evaluated, and their structure-activity relationships were summarized. Among them, C16 exhibited the most potent inhibitory activity, as evidenced by its IC50 values ranging from 0.5-2.5 µM for inhibiting sphere formation and 0.5-15 µM for cytotoxicity. Furthermore, we found that C16 could hinder tumorigenesis and migration and promote apoptosis in vitro. These effects were attributed to the downregulation of stem-related genes. The in vivo evaluation demonstrated that C16 exhibited efficient permeability across the blood-brain barrier and potent efficacy in both subcutaneous and orthotopic glioma tumor models. Hence, C16 may serve as a potential lead compound targeting ZNF207 and has promising therapeutic potential for glioma.
Asunto(s)
Antineoplásicos , Glioma , Humanos , Glioma/tratamiento farmacológico , Glioma/patología , Relación Estructura-Actividad , Apoptosis , Benzamidas/farmacología , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proliferación Celular , Proteínas Asociadas a MicrotúbulosRESUMEN
ReNiO3 (Re = Pr, Sm, Eu) solid electrolytes were prepared by the sol-gel method, which were sintered in a pure oxygen atmosphere of 20 MPa at 1000 °C for 24 hours. The DC resistivities of the three materials in air and in a hydrogen-containing atmosphere were tested respectively. The resistivities in the hydrogen-containing atmosphere were about 102, 104, and 105 times higher than those in air and XPS analysis showed that after 10%H2-Ar treatment, the proportion of Ni2+ of PrNiO3, SmNiO3 and EuNiO3 increased successively. The proton transport number of PrNiO3 was lower than 0.5 at 50-500 °C, and SmNiO3 and EuNiO3 were almost pure proton conductors below 200 °C. The conductivities of SmNiO3 and EuNiO3 were 1.08 × 10-4 S cm-1 and 1.83 × 10-5 S cm-1 at 200 °C in 5%H2-Ar. The hydrogen sensing properties of SmNiO3 and EuNiO3 show that the measurement results of the two materials were accurate in the range of 0.5-10% H2.