RESUMEN
In the late 1960s, the steroidal alkaloid cyclopamine was isolated from the plant Veratrum californicum and identified as the teratogen responsible for craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in the western United States. Cyclopamine was found to inhibit the hedgehog (Hh) signaling pathway, which plays a critical role in embryonic development. More recently, aberrant Hh signaling has been implicated in several types of cancer. Thus, inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. A brief history of cyclopamine and cyclopamine derivatives investigated for the treatment of cancer is presented.
Asunto(s)
Neoplasias/tratamiento farmacológico , Extractos Vegetales/farmacología , Oveja Doméstica/anomalías , Alcaloides de Veratrum/toxicidad , Veratrum/química , Alimentación Animal/análisis , Alimentación Animal/toxicidad , Animales , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Holoprosencefalia/inducido químicamente , Holoprosencefalia/patología , Humanos , Mutación , Extractos Vegetales/química , Transducción de Señal , Teratógenos/toxicidad , Alcaloides de Veratrum/químicaRESUMEN
[reaction: see text] The expedient synthesis of a library of kanamycin B analogues is reported. The revealed SAR will guide future designs in developing kanamycin-type aminoglycoside antibiotics against drug-resistant bacteria.