mercaptopurine and allicin

S-allylthio-6-mercaptopurine and its ribose derivative were tested for anti-leukemic activity, using a human- mouse B-CLL model. The novel prodrugs contain two components, a purine analog, which interferes with DNA synthesis, and an S-allylthio, readily engaging in thiol-disulfide exchange reactions. The latter component targets the redox homeostasis which is more sensitive in leukemic cells, than in normal B-cells. Upon administration, the prodrug permeates cells, instantly reacts with free thiol, forming S-allyl mixed disulfides and releasing purine. Several cycles of thiol-disulfide exchange reactions occur, thus extending the duration of the prodrug effects. The concerted action of 2 components, as compared with purine alone, boosted in vitro apoptotis in B-CLL cells from 10% to 38%, and decreased in vivo engraftment of B-CLL from 30% to 0.7%.

Topics: Allyl Compounds; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; B-Lymphocytes; Cell Membrane Permeability; Disease Models, Animal; Disulfides; DNA; Drug Synergism; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Mercaptopurine; Mice; Mice, Inbred ICR; Oxidation-Reduction; Prodrugs; Sulfhydryl Compounds; Sulfinic Acids