Novel Isopentenyladenosine analogues: synthesis and evaluation of antiproliferative activity

N6-isopentenyladenosine(iPA) is able to inhibit protein prenylation and competes for nucleoside transport. It has been shown that iPA exerts a potent in vitro anticancer activity while it has a slight effect on tumor growth in rodents. This lack of in vivo activity could be due to the short plasma half-life of iPA as it is wellknown for other nucleosides. To identify compounds endowed with in vitro and antiproliferative activity, we have investigated structural modificationa of iPA. We synthesized acyclonucleosides characterized by the presence of an acyclic component, structurally resembling part of the ribose moiety in iPA. Then we synthesized iPA analogues in which thw hydroxyl groups were replaced by an hydrogen group in order to verify the importance of each hydroxyl group of the furanosidic moiety for the activity of iPA.Lastly we also synthesized iPA analogues in which the N6-position was differently subsituted with the aim of verify the importance of the isopentenyl chain for the activity of the molecule. All compounds were in vitro tested using different cell lines and the proliferation assay was carried out in the presence and absence of serum.