RESUMEN
Novel C4-benzazole naphthalimide derivatives were synthesized and tested in vitro and in vivo as anti-cancer drugs. Among these synthetic molecules, compounds 9 and 10 exhibited cytotoxicity against murine B16F10 melanoma cells. In addition, the above-mentioned compounds significantly suppressed lung tumor metastasis with no visible sign of toxicity.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Melanoma/tratamiento farmacológico , Naftalimidas/farmacología , Inhibidores de Topoisomerasa II/farmacología , Animales , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Melanoma/metabolismo , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Naftalimidas/síntesis química , Naftalimidas/química , Relación Estructura-Actividad , Inhibidores de Topoisomerasa II/síntesis química , Inhibidores de Topoisomerasa II/químicaRESUMEN
The antioxidant ability of an array of commercially available flavonoids was evaluated on the larvae of the zebrafish model organism, in order to find flavonoids with lower toxicities and higher radical oxygen-scavenging properties than flavone. Among the flavonoids tested, chrysin and morin possessed higher reactive oxygen species (ROS)-scavenging rates (-99% and -101%, respectively) and lower toxicity (LD(50)>100 ppm). Zebrafish fins in the UVB+chrysin group were 6.30 times more likely to grow to normal fin size than those in the UVB-only control group, while zebrafish fins in the UVB+morin group were 11.9 times more likely to grow to normal fin size than those in the UVB-only control group. These results were analysed by the QSAR method and were in accordance with predicted values. A new 4'-fluoroflavone was synthesised. The ROS-scavenging rate of 4'-fluoroflavone was -54%, which corresponds well with the predicted value (-48%). We propose that a combination of QSAR prediction and the zebrafish model organism is efficient for evaluating new flavonoids.
Asunto(s)
Antioxidantes/química , Antioxidantes/toxicidad , Flavonoides/química , Flavonoides/toxicidad , Larva/efectos de los fármacos , Animales , Bioensayo , Flavonas/química , Flavonas/toxicidad , Relación Estructura-Actividad , Pez Cebra/embriologíaRESUMEN
We described herein a concise synthesis of 3',4'-diaminoflavone 10. This new, three-step synthetic approach is more efficient than the conventional seven-step synthetic method. The route is shortened significantly by introducing the amino moieties early and eliminating the need for nitro group reduction. The other two analogues, 5,7-dihydroxy-3',4'-diaminoflavone 11 and 5,7-dimethoxy-3',4'-diaminoflavone 12, were also synthesized similarly. The above three compounds, along with flavone, were evaluated for their antioxidant and UVB-protection abilities on zebrafish larvae. The data showed that compound 10 exhibited the best result, with -102.3% of ROS-scavenging rate.