Asunto(s)
Adenosina Desaminasa/inmunología , Proteinosis Alveolar Pulmonar/inmunología , Adenosina Desaminasa/genética , Adenosina Desaminasa/uso terapéutico , Animales , Terapia de Reemplazo Enzimático , Ratones , Ratones Mutantes , Proteinosis Alveolar Pulmonar/tratamiento farmacológico , Proteinosis Alveolar Pulmonar/enzimología , Proteinosis Alveolar Pulmonar/genética , Proteinosis Alveolar Pulmonar/patologíaRESUMEN
A series of substituted styryl-acrylonitriles was designed and synthesized. The new compounds, called tyrenes, were tested for the ability to inhibit acute lymphocytic leukemia (ALL) cancer cell growth, as well as on their toxicity to normal bone marrow (NBM) cells. The results showed that 3,4-dihydroxystyryl-acrylonitriles, in particular CR-4, revealed great potency as antitumor agents, and also exhibited low toxicity to normal cells. The effectiveness of these compounds with extended conjugation may be due to their possible functioning as reactive Michael acceptors.
Asunto(s)
Acrilonitrilo/análogos & derivados , Acrilonitrilo/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Estirenos/química , Estirenos/farmacología , Acrilonitrilo/metabolismo , Antineoplásicos/química , Línea Celular Tumoral , Humanos , Estirenos/síntesis químicaRESUMEN
In recent years, synthetic tyrosine kinase inhibitors have made a rapid transition from basic research to therapeutic application. These compounds represent a major clinical advance in the approach to cancer in their relative specificity of action and decreased toxicity. We report here the effects of a novel tyrosine kinase inhibitor CR4 that interferes with growth-promoting pathways to markedly inhibit the growth and survival of both Philadelphia-positive and -negative acute lymphoblastic leukemia (ALL) as well as acute myeloid leukemia (AML). While efficiently ablating leukemic cell growth, normal cell growth and differentiation remain unaffected by CR4. CR4 demonstrates an ability to inhibit the function of multiple growth-critical kinases and yet exhibits a low level of cytotoxicity. These findings suggest that CR4 may prove to be highly effective as a therapeutic agent.