Human and animal leukemias, varying widely in responsive ness to 6-mercaptopurine, were examined to seek determinants of drug sensitivity. Drug-responsive rodent leukemias showed a comparatively high capacity for in vitro conversion of 6-mer captopurine into nondiffusible cellular metabolites, predomi nantly drug nucleotides. A similar study of human leukemia cells indicated that the in vitro c...

BACKGROUND Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drug delivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs. METHODS AND RESULTS We synthesized superparamagnetic nanoparticles containing pure iron...

Several 9-alkyl, 6-thiopurines have been reported to have more favorable therapeutic indexes than do the parent drugs, 6-mercaptopurine (MP) and 6-thioguanine (TG). Some of these compounds were reported to be active against cells in culture resistant to 6-thiopurines, and it has been assumed that their mechanisms of action may differ from those of TG and MP. 9-(n-Butyl)-6-thioguanine was essent...

Twenty-two adult patients with acute nonlymphocytic leukemia received daunorubicin, and 21 received a combina tion of prednisone, vincristine, 6-mercaptopurine, and methotrexate in a randomized study. The single agent was superior to the combination in inducing complete remission (50 versus 28%). In addition, patients who completely responded to daunorubicin did so in a median of 19 days, where...

BACKGROUND Mercaptopurine is a prodrug requiring intracellular activation to thiopurine nucleotides to exert antileukemic effect. We developed a reversed-phase liquid chromatographic assay for the quantification of mercaptopurine, thioguanine, and methylmercaptopurine nucleoside and nucleotide concentrations in the target tissue, the leukemic lymphoblast. METHODS Leukemic blasts were isolated...

The transforming activity of DMA isolated from 6-mercaptopurine-treated cultures of Bacillus subtilis strain UTH-8505 is markedly reduced when compared to that of DMA obtained from control cultures. The lower transforming activity appears to be a property of the isolated DNA; i.e., various treatments either to restore the activity or to indicate the presence of inhibitory substances that isolat...

6- mercaptopurine (6-mp) is widely used in clinic as an immunosuppressive for treatment of acute lymphocytic leukemia, crohn's disease, and ulcerative colitis with documented unpredictable hepatotoxicity. the potential molecular cytotoxic mechanisms of 6-mp against isolated rat hepatocytes were searched in this study using “accelerated cytotoxicity mechanism screening (acms)” techniques. t...

6-Mercaptopurine was found to inhibit the growth of cultured human lymphoma P3HR-1 cells and the incorporation of [3H]-uridine into trichloroacetic acid-precipitable materials of the cells. One of the derivatives of 6-mercaptopurine, 6-mercaptopurine ribonucleoside triphosphate (6-thio-ITP), was found to inhibit in vitro RNA synthesis (both engaged and free enzyme activities) of the isolated nu...

In this study, we repositioned thiopurine drugs used for the treatment of acute 12 leukaemia as new tyrosinase inhibitors. Tyrosinase catalyses two distinct and successive 13 oxidations in melanin biosynthesis: the conversions of tyrosine to dihydroxyphenylalanine (DOPA) 14 and DOPA to dopaquinone. Continuous efforts are underway to discover small molecule 15 inhibitors of tyrosinase for therap...

A study of the degree of reproducibility of the Carcinoma 755 system when employed to obtain therapeutic indices of purine antagonists has been carried out. Some 60 "active" purine analogs have been studied by this system, used in a quantitative manner, and the approximate LD10's, minimum effective doses, therapeutic indices (LD10/T/C 0.10), and maximum degrees of effectiveness (T/C at the LD10...