RESUMEN
Several flavonoid-like compounds were found to possess good antiproliferative properties. Herein, we examined the ability of four naturally occuring and biologically active flavonoids from the genus Dorstenia, gancaonin Q (1), 6-prenylapigenin (2), 6,8-diprenyleriodictyol (3), and 4-hydroxylonchocarpin ( 4), to inhibit the proliferation of a panel of fourteen cancer cell lines including leukemia and solid cancer cells, as well as AML12 normal hepatocytes. The study was extended to the analysis of cell cycle distribution, apoptosis induction, and caspase 3/7 activity and the antiangiogenic properties of the four compounds. The results of the cytotoxicity assays showed that more than 50â% inhibition of proliferation was obtained with compound 1 on all the fourteen studied cancer cell lines, with IC (50) values below 20 µg/mL. Compounds 2, 4, and 3 showed selective activity, with IC (50) values below 20 µg/mL being noted on 57.15â%, 71.42â%, and 85.71â% of the fourteen cancer cell lines, respectively. None of the compounds exhibited more than 50â% inhibition against AML12 normal hepatocytes cells at 20 µg/mL. IC (50) values below or around 4 µg/mL were recorded on 28.57â% of the tested cell lines for both compound 1 and 4 and 21.43â% for compound 3, which appeared to be the best cytotoxic compounds. This study indicates that caspase 3/7 activation is one of the modes of induction of apoptosis for compounds 1, 3, and 4 in CCRF-CEM cells. The results of the antiangiogenic assay indicated that compounds 1, 3, and 4 were also able to inhibit the growth of blood capillaries on the chorioallantoic membrane of quail eggs, the best effect being noted for compound 4 (54.1â% inhibition). The results of the present work provide evidence of the cytotoxic potential of the four studied flavonoids and supportive data for further investigations.
Asunto(s)
Flavonas/farmacología , Flavonoides/farmacología , Moraceae/química , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Caspasa 3/química , Caspasa 7/química , Ciclo Celular , Supervivencia Celular , Embrión de Pollo , Membrana Corioalantoides/efectos de los fármacos , Doxorrubicina/farmacología , Activación Enzimática , Flavonas/química , Flavonoides/química , Células HeLa , Hepatocitos/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Moraceae/toxicidad , Neovascularización Patológica/tratamiento farmacológico , Oxazinas/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Codorniz , Relación Estructura-Actividad , Factores de Tiempo , Xantenos/química , Cigoto/efectos de los fármacosRESUMEN
O estudo químico, biológico, farmacológico e toxicológico de plantas empregadas como medicamentosas por diferentes populações vem sendo incrementado ao longo dos anos, principalmente na busca de novos medicamentos, quer eles sejam fitoterápicos, homeopáticos ou alopáticos.Envolvido por esse mesmo interesse,buscamos desenvolver pesquisas com a planta brasileira Brosimum gaudichaudii Trecul (Moraceae), entre outras, a qual ocorre nos campos e cerrados e mata mesofítica do país.Com tal finalidade foram obtidosdiferentes extratos, separadas frações, isoladas substâncias, principalmente cumarinas e determinadas as respectivas estruturas empregando métodos espectrométricos e outros.Com a colaboração de outros pesquisadores foi possível realizar diferentes ensaios biológicos e mesmo pesquisa clínica básica, a saber:determinação das atividades anti-helmíntica, antimicrobiana, fotossensibilizante, anticancerígena, toxicológica, mutagênica e estudo patogenético, com a finalidade de se chegar a um medicamento genuinamente brasileiro, seja fitoterápico, seja homeopático.