RESUMEN

The anti-proliferative effects of a novel bromomethoxylated arylphosphate derivative of zidovudine (compound DDE46, CAS 213982-96-8) were first examined in a zebra fish embryo model. DDE46 blocked the cell division at the 2-cell stage of the embryonic development followed by total cell fusion. DDE46 also inhibited the proliferation of the leukemic cell lines NALM-6 and MOLT-3. DDE46 enhanced the activity of the pro-apoptotic enzymes Caspase-3, Caspase-6, Caspase-8, and Caspase-9 leading to the apoptotic death of the leukemic cell line Jurkat. These results justify the further development of this agent as a new anti-leukemic drug candidate.

Asunto(s)

Antineoplásicos/farmacología , Leucemia/tratamiento farmacológico , Timidina Monofosfato/análogos & derivados , Timidina Monofosfato/farmacología , Zidovudina/análogos & derivados , Zidovudina/farmacología , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Inhibidores de Caspasas , Proliferación Celular/efectos de los fármacos , Didesoxinucleótidos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células Jurkat , Espectroscopía de Resonancia Magnética , Nefelometría y Turbidimetría , Profármacos/farmacología , Sales de Tetrazolio , Tiazoles , Tubulina (Proteína)/biosíntesis , Tubulina (Proteína)/genética , Pez Cebra