ANTICANCER PYRIMIDINE ACYCLONUCLEOSIDES

Several acyclonucleosides have been synthesized. Series 8 could libera te 5-FU and acrolein selectively in the tumour tissue whilst 9 only di scharge 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 mim ics the conformational structure of the sugar of desoxyuridine. Biolog ical assays have been carried out in vitro on tumour growth in Ehrlich ascitic cells with the consequent decrease of 35% in the cellular mit osis. IC50 showed values between 3-45 mu M 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.