RESUMO

METHODS: The synthesis of conjugates of flutamide with resorcinarene-PAMAM-dendrimers as well as alkyl and ethyl phenyl chains in the lower part of the macrocycle as a nucleus and diethylenetriamines in the dendritic branches gives the opportunity to obtain conjugates in one step of synthesis with 16 and 64 flutamide moieties in the structure. RESULTS: The in vitro anticancer studies showed that the conjugates of flutamide are more active than the free flutamide and the flutamide derivatives, thus diminishing the amount of flutamide used. The resorcinarenedendrimer- flutamide conjugates with a high drug payload improve the activity of the drug. CONCLUSION: This is important in delivering a sufficient amount of flutamide and suggests that the dendrimer facilitates more of the drug being introduced into cells. It was also observed that the new conjugates are less toxic than the anti-androgens.

Assuntos

Antineoplásicos/farmacologia , Calixarenos/farmacologia , Dendrímeros/farmacologia , Portadores de Fármacos/farmacologia , Flutamida/farmacologia , Fenilalanina/análogos & derivados , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Calixarenos/síntese química , Calixarenos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dendrímeros/síntese química , Dendrímeros/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Flutamida/síntese química , Flutamida/química , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Fenilalanina/síntese química , Fenilalanina/química , Fenilalanina/farmacologia