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Journal of Immunological Methods 1981Primed syngeneic or unprimed allogeneic mouse spleen cells were stimulated with azaguanine-resistant P815 tumor cells that were killed by the addition of aminopterin to...
Primed syngeneic or unprimed allogeneic mouse spleen cells were stimulated with azaguanine-resistant P815 tumor cells that were killed by the addition of aminopterin to the stimulation medium. The recovery of lymphocytes and their cytolytic activity and specificity were similar to those obtained after stimulation with irradiated cells. This method conveniently replaces the inactivation of stimulatory cells by irradiation or mitomycin treatment. Moreover, it has the advantage of inactivating not only the stimulatory cells but also the tumor cells that often contaminate the spleens of tumor-bearing animals, provided these animals have been inoculated with azaguanine-resistant tumor cell mutants.
Topics: Aminopterin; Animals; Azaguanine; Cell Transformation, Neoplastic; Culture Media; Cytotoxicity, Immunologic; Hypoxanthines; Mast-Cell Sarcoma; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mutation; T-Lymphocytes; Thymidine
PubMed: 6796623
DOI: 10.1016/0022-1759(81)90317-3 -
Antimicrobial Agents and Chemotherapy Apr 2018The high acquisition rate of drug resistance by necessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for...
The high acquisition rate of drug resistance by necessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for the treatment of other diseases have the potential to be repurposed for the treatment of TB. In this study, a high-throughput screening of compounds against thiol-deficient strains and subsequent validation with thiol-deficient strains revealed that and mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su); and mutants had increased susceptibility to bacitracin (Ba); and , , and mutants had increased susceptibility to fusaric acid (Fu). Further analyses revealed that some of these compounds were able to modulate the levels of thiols and oxidative stress in This study reports the activities of Aza, Su, Fu, and Ba against and provides a rationale for further investigations.
Topics: Antitubercular Agents; Azaguanine; Mutation; Mycobacterium tuberculosis; Oxidative Stress; Sulfaguanidine; Sulfhydryl Compounds
PubMed: 29437626
DOI: 10.1128/AAC.02236-17 -
Journal of Biomolecular Structure &... 2014Analogues of purine bases are highly relevant in the biological context and have been implicated as drug molecules for therapy against a number of diseases....
Analogues of purine bases are highly relevant in the biological context and have been implicated as drug molecules for therapy against a number of diseases. Additionally, these molecules have been implicated to have a role in the prebiotic RNA world. However, experimental data on the structures of these molecules in aqueous solution is lacking. In this work, we report the ultraviolet resonance Raman spectra of 6-chloroguanine, 8-azaguanine and allopurinol, obtained with 260 nm excitation. The reported spectra have been assigned to normal modes computed from density functional theory (B3LYP/6-31G (d,p)) calculations. This work has been useful in identifying the solution-state structures of these molecules at neutral pH. We find that the guanine analogues 6-chloroguanine and 8-azaguanine exist as keto-N9H and keto-N7H tautomers in solution, respectively. On the other hand, the hypoxanthine analogue allopurinol exists as a mixture of keto-N9H and keto-N8H tautomers in solution. We predict that this work would be particularly useful in future vibrational studies where these molecules are present in complexes with their target proteins.
Topics: Allopurinol; Azaguanine; Guanine; Hydrogen-Ion Concentration; Molecular Structure; Spectrum Analysis, Raman
PubMed: 23384120
DOI: 10.1080/07391102.2012.745821 -
The Journal of Antibiotics Jun 1978
Topics: Azaguanine; Culture Media; Guanine; Streptomyces
PubMed: 681246
DOI: 10.7164/antibiotics.31.628 -
The Biochemical Journal May 1964
Topics: Antimetabolites; Azaguanine; In Vitro Techniques; Pseudomonas aeruginosa; Triazoles; Uric Acid; Xanthine Oxidase; Xanthines
PubMed: 4953816
DOI: 10.1042/bj0910270 -
Blood May 1955
Topics: Azaguanine; Guanine; Leukemia
PubMed: 14363328
DOI: No ID Found -
Mutation Research Jan 1981The cytotoxic effects of azaguanine and thioguanine have been compared in two wild-type V79 cells. To achieve equitoxic effects in both cell lines a 10-20-fold higher...
The cytotoxic effects of azaguanine and thioguanine have been compared in two wild-type V79 cells. To achieve equitoxic effects in both cell lines a 10-20-fold higher concentration of azaguanine than thioguanine was required. Affinity of HGPRT for azaguanine was 10-fold lower than for hypoxanthine in both cell lines and was similar to that for thioguanine in V79S cells. Affinity for thioguanine differed by a factor of 3 in the two cell lines. The rate of cell kill by azaguanine was markedly slower than by thioguanine in both cell lines. Reduction of whole cell uptake of [14C]hypoxanthine incorporation by unlabelled azaguanine was only demonstrable after prolonged incubation periods as was incorporation of [14C]azaguanine into acid-insoluble material. Experiments with cell-free extracts indicated that hypoxanthine acts as a non-competitive inhibitor of the enzyme. The slow rate of dissociation of the HGPRT-azaguanine complex is reflected in the slow rate of killing of wild-type cells. Clones resistant to the cytotoxic effects of these analogues have been selected from both cell lines and have been shown to possess HGPRT with altered kinetic properties. Our data suggest that azaguanine and thioguanine may select for mutations at different sites on the HGPRT molecule in V79 cells and provide possible explanations for the differences in effectiveness of these two agents reported in other cell lines.
Topics: Animals; Azaguanine; Cell Line; Cricetinae; Cricetulus; Genes; Hypoxanthine Phosphoribosyltransferase; Lung; Mutagens; Mutation; Thioguanine
PubMed: 7207481
DOI: 10.1016/0027-5107(81)90186-x -
Journal of Bacteriology May 1966Stahly, D. P. (University of Illinois, Urbana), V. R. Srinivasan, and H. Orin Halvorson. Effect of 8-azaguanine on the transition from vegetative growth to...
Stahly, D. P. (University of Illinois, Urbana), V. R. Srinivasan, and H. Orin Halvorson. Effect of 8-azaguanine on the transition from vegetative growth to presporulation in Bacillus cereus. J. Bacteriol. 91:1875-1882. 1966.-The guanine analogue, 8-azaguanine (azaG), was found to inhibit sporulation of Bacillus cereus strain T when added to proliferating cells, but not to inhibit when added after the transition to presporulation. When azaG was added to vegetative cells, the growth rate was reduced, but no immediate bactericidal effect was demonstrated. Azaguanine was shown to be incorporated solely into ribonucleic acid (RNA). All of the natural purine bases and nucleosides were found to prevent azaG inhibition by blocking incorporation of the analogue into the RNA. Addition of a subinhibitory level of C(14)-azaG to proliferating cells resulted in an increase in incorporation paralleling the increase in number of cells. At the time of transition from growth to presporulation, a rapid removal of the azaG label from the cells occurred in the absence of net RNA breakdown. If differentiation was inhibited by increasing the concentration of azaG, then no expulsion took place. Instead, at the end of growth, net incorporation ceased, and a steady-state condition was established in which incorporation equaled breakdown. No azaG degradative enzymes are present in presporulating cells. The possibility is discussed that an increase in the ratio of natural purines to azaG occurred at the time of transition, and that the natural purine derivatives then were reincorporated into RNA preferentially to azaG. The data are consistent with the hypothesis than an increased rate of RNA turnover occurs at the time of transition from vegetative growth to presporulation. Addition of phosphate buffer (pH 7.0, 0.1 m) to azaG-inhibited vegetative cells caused reversal of inhibition, the reversal being accompanied by expulsion of the azaG. At least a partial explanation of this effect is that phosphate causes a decrease in the azaG intracellular pool size.
Topics: Azaguanine; Bacillus cereus; Carbon Isotopes; Colorimetry; Drug Resistance, Microbial; In Vitro Techniques; Purines; Pyrimidines; RNA, Bacterial
PubMed: 4957026
DOI: 10.1128/jb.91.5.1875-1882.1966 -
Genetics Jun 1970
Topics: Aminopterin; Animals; Azaguanine; Cell Line; Chromosomes; Colchicine; Culture Techniques; Hypoxanthines; Mice; Mutation; Thymidine; Transferases
PubMed: 5474829
DOI: 10.1093/genetics/65.2.279 -
Applied Microbiology Jan 1968
Topics: Azaguanine; Leptospira; Leptospira interrogans; Water Microbiology
PubMed: 5636463
DOI: 10.1128/am.16.1.174-175.1968