Pharmacogenomics and analogues of the antitumour agent N 6 ‐isopentenyladenosine

N 6 ‐isopentenyladenosine (i 6 A), a member of the cytokinin family of plant hormones, has potent in vitro antitumour activity in different types of human epithelial cancer cell lines. Gene expression profile analysis of i 6 A‐treated cells revealed induction of genes ( e.g ., PPP1R15A, DNAJB9, DDIT3, and HBP1) involved in the negative regulation of cell cycle progression and reportedly up‐regulated during cell cycle arrest in stress conditions. Of 6 i 6 A analogues synthesized, only the 1 with a saturated double bond of the isopentenyl side chain had in vitro antitumour activity, although weaker than that of i 6 A, suggesting that i 6 A biological activity is highly linked to its structure. In vivo analysis of i 6 A and the active analogue revealed no significant inhibition of cancer cell growth in mice by either reagent. Thus, although i 6 A may inhibit cell proliferation by regulating the cell cycle, further studies are needed to identify active analogues potentially useful in vivo . © 2008 Wiley‐Liss, Inc.