Synthesis and evaluation of new 5-fluorouracil antitumor cell differentiating derivatives.
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.
Domínguez
José F
JF
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
Marchal
Juan A
JA
Correa
Antonio
A
Carrillo
Esmeralda
E
Boulaiz
Houria
H
Aránega
Antonia
A
Gallo
Miguel A
MA
Espinosa
Antonio
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry / Q000379:methods; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects; D008858:Microscopy, Phase-Contrast; D011355:Prodrugs / Q000494:pharmacology; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011355:Prodrugs; D013940:Thymidylate Synthase; D005472:Fluorouracil