Novel isopentenyladenosine analogues: synthesis, characterization, and evaluation of antiproliferative activity on bladder carcinoma cells.
Isopentenyladenosine (iPA), a member of the cytokinin family of plant hormones, exerts a marked antiproliferative activity on some leukemic and epithelial cancer cell lines. To characterize the molecular moieties required for the in vitro antitumor activity of the molecule and to obtain cytostatic iPA derivatives potentially useful as chemotherapeutic agents, N9-acyclic analogues have been synthesized using regioselective Mitsunobu reaction and characterized by elemental analyses, (1)H and (13)C NMR. These compounds were analyzed for their activity on human bladder cancer cell lines. In this study, we report that iPA inhibited the proliferation but not the migration of human bladder cancer cells, while the newly synthesized analogues revealed no significant cytostatic activity apart from the compound with a saturated double bond of the isopentenyl chain. These results indicate that the integrity of the ribose ring is required for the cytostatic activity of iPA.
Ottria
Roberta
R
Dipartimento di Scienze Precliniche LITA Vialba-Universita degli Studi di Milano, Milano, Italy.
Casati
Silvana
S
Maier
Jeanette A M
JA
Mariotti
Massimo
M
Ciuffreda
Pierangela
P
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D007541:Isopentenyladenosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D007541:Isopentenyladenosine