Synthesis and evaluation of new 5-fluorouracil antitumor cell differentiating derivatives |
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Authors: | Domínguez José F Marchal Juan A Correa Antonio Carrillo Esmeralda Boulaiz Houria Aránega Antonia Gallo Miguel A Espinosa Antonio |
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Affiliation: | Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Granada, Spain. |
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Abstract: | Three new antitumour drugs containing two 5-fluorouracil moieties at both ends of the structure and a two amide bond linker were synthesized. Appropriated bis-acetal were reacted with two equivalents of 5-FU to afford the desired compounds. These drugs were evaluated for their ability to induce myogenic maturation in vitro on human rhabdomyosarcoma cells in an experimental model. Compounds 5 and 6 induced morphological and phenotypical differentiation in rhabdomyosarcoma cells at 4.5 and 3.5 microM, respectively. These new cell differentiating agents could be used as an alternative to selective destruction of undifferentiated cells. A potential role of the differentiation therapy as an alternative approach to the treatment of rhabdomyosarcomas is suggested. |
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