Anticancer pyrimidine acyclonucleosides.
Several acyclonucleosides have been synthesized. Series 8 could liberate 5-FU and acrolein selectively in the tumour tissue whilst 9 only discharge 5-FU. The conformational analysis of 8 and 9 has been carried out by means of Molecular Mechanics, using the MM2 force field. It was observed that the open chain linked to the N-1 of the 5-FU moiety mimics the conformational structure of the sugar of desoxyuridine. Biological assays have been carried out in vitro on tumour growth in Ehrlich ascitic cells with the consequent decrease of 35% in the cellular mitosis. IC50 showed values between 3-45 microM for series 8 whilst series 9 were less active than 5-FU. Compared with that of 5-FU the acute and chronic toxicity is considerably decreased.
Gallo-Mezo
M A
MA
Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Granada, Spain.
Espinosa
A
A
Campos
J
J
Entrena
A
A
Pineda de las Infantas
M J
MJ
Gómez
J A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D015195:Drug Design; D006801:Humans; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D000970:Antineoplastic Agents; D011743:Pyrimidines