Development of Amino Acid Prodrugs of Cytarabine

Cytarabine is widely used in chemotherapy for different types of leukemia due to the targeting effects on cells in the S phase of cell cycle. However, its use is limited by its poor absorption and fast degradation to biologically inactive forms, and elimination. Amino acid (isoleucine and valine) prodrugs of cytarabine were synthesized to improve uptake of cytarabine. The prodrugs may also reduce the proportion of the drug that was degraded and increase bioavailability. Stability and permeability studies performed with cytarabine prodrugs demonstrated improved uptake. Cytotoxic studies utilizing K562 cell lines revealed 4.5% greater growth inhibition at 24 hours incubation and 19% greater growth inhibition at 72 hours incubation with the cytarabine isoleucine prodrug than with cytarabine. The results indicated that the prodrug may work more efficiently than the parent drug.