RESUMEN
Examples of organometallic compounds as nucleoside analogues are rare within the field of medicinal bioorganometallic chemistry. We report on the synthesis and properties of two chiral ferrocene derivatives containing a nucleobase and a hydroxyalkyl group. These so-called ferronucleosides show promising anticancer activity, with cytostatic studies on five different cancer cell lines indicating that both functional groups are required for optimal activity.
Asunto(s)
Compuestos Ferrosos/química , Nucleósidos/síntesis química , Compuestos Organometálicos/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Compuestos Ferrosos/farmacocinética , Humanos , Leucemia L1210/tratamiento farmacológico , Metalocenos , Nucleósidos/farmacología , Compuestos Organometálicos/químicaRESUMEN
Iron plays a crucial role in a number of metabolic pathways including oxygen transport, DNA synthesis, and ATP generation. Although insufficient systemic iron can result in physical impairment, excess iron has also been implicated in a number of diseases including ischemic heart disease, diabetes, and cancer. Iron chelators are agents which bind iron and facilitate its excretion. Experimental iron chelators have demonstrated potent anti-neoplastic properties in a number of cancers in vitro. These agents have yet to be translated into clinical practice, however, largely due to the significant side effects encountered in pre-clinical models. A number of licensed chelators, however, are currently in clinical use for the treatment of iron overload associated with certain non-neoplastic diseases. Deferasirox is one such agent and the drug has shown significant anti-tumor effects in a number of in vitro and in vivo studies. Deferasirox is orally administered and has demonstrated a good side effect profile in clinical practice to date. It represents an attractive agent to take forward into clinical trials of iron chelators as anti-cancer agents.