3-amino-1,2,4-triazole inhibits macrophage NO synthase.

Murine macrophages activated by interferon-gamma and lipopolysaccharide become leishmanicidal through a process involving L-arginine-derived nitrogen oxidation products. Both nitrite secretion and parasite killing by activated macrophages were inhibited by 3-amino-1,2,4-triazole as well as the related compound, 3-amino-1,2,4-triazine. Moreover, NO synthase activity in cytosolic extracts of activated cells was inhibited by both compounds. 4-amino-1,2,4-triazole, an isomer of 3-amino-1,2,4-triazole, was without effect. Our results suggest that besides its known inhibitory effect on catalases and peroxidases, 3-amino-1,2,4-triazole is an inhibitor of NO synthase. The resemblance between the tautomeric form of 3-amino-1,2,4-triazole and the guanidino group of L-arginine, the natural substrate for NO synthase, might be responsible for the observed inhibition.     

Au-nanoclusters incorporated 3-amino-5-mercapto-1,2,4-triazole film modified electrode for the simultaneous determination of ascorbic acid, dopamine, uric acid and nitrite

A novel biosensor has been constructed by the electrodeposition of Au-nanoclusters (nano-Au) on poly(3-amino-5-mercapto-1,2,4-triazole) (p-TA) film modified glassy carbon electrode (GCE) and employed for the simultaneous determination of dopamine (DA), ascorbic acid (AA), uric acid (UA) and nitrite (NO₂⁻). NH₂ and SH groups exposed to the p-TA layer are helpful for the electrodeposition of nano-Au. The combination of nano-Au and p-TA endow the biosensor with large surface area, good biological compatibility, electricity and stability, high selectivity and sensitivity and flexible and controllable electrodeposition process. In the fourfold co-existence system, the linear calibration plots for AA, DA, UA and NO₂⁻ were obtained over the range of 2.1–50.1 μM, 0.6–340.0 μM, 1.6–110.0 μM and 15.9–277.0 μM with detection limits of 1.1 × 10⁻⁶ M, 5.0 × 10⁻⁸ M, 8.0 × 10⁻⁸ M and 8.9 × 10⁻⁷ M, respectively. In addition, the modified biosensor was applied to the determination of AA, DA, UA and NO₂⁻ in urine and serum samples by using standard adding method with satisfactory results.     

Histamine-like stimulator of gastric secretion--3-(beta-aminoethyl)-5-amino-1,2,4-triazole]

3-(beta-aminoethyl)-5-amino-1,2,4-triazol or IEM-759 acts predominantly on the histamine H2-receptors in the dog stomach. It produces a lesser effect on the H1-histamine-sensitive receptors of the intestine, vessels and bronchi than histamine. Unlike histalog, IEM-759 taken per os is also effective, this pointing to a possibility of its use in gastoenterology for the assay of secretory capacity of the stomach.     

Inhibition of some hepatic glycosidases by the diseco nucleoside, 4-amino-3-(D-glucopentitol-1-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analog

The in vivo and in vitro effects of 4-amino-3-(D-glucopentitol-1-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analogue on alpha- and beta-glucosidases, beta-glucuronidase as well as alpha-amylase have been investigated. alpha-Glucosidase is the enzyme that is markedly affected in vivo and in vitro in a dose-dependent manner. The compounds showed a reversible inhibition of a competitive type for alpha-glucosidase. Moreover, they exert a relatively potent inhibition on alpha-glucosidase with a Ki magnitude of 3.6 x 10(-4), 9.5 x 10(-5) M.     

Effect of catalase-specific inhibitor 3-amino-1,2,4-triazole on yeast peroxisomal catalase in vivo

3-Amino-1,2,4-triazole (3-AT) is known as an inhibitor of catalase to whose active center it specifically and covalently binds. Subcellular fractionation and immunoelectronmicroscopic observation of the yeast Candida tropicalis revealed that, in 3-AT-treated cells in which the 3-AT was added to the n-alkane medium from the beginning of cultivation, catalase transported into peroxisomes was inactivated and was present as insoluble aggregated forms in the organelle. The aggregation of catalase in peroxisomes occurred only in these 3-AT-treated cells and not in cells in which 3-AT was added at the late exponential growth phase. Furthermore, 3-AT did not affect the transportation of catalase into peroxisomes. The appearance of aggregation only in cells to which 3-AT was added from the beginning of cultivation suggests that, in the process of catalase transportation into yeast peroxisomes, some conformational change may take place and that correct folding may be inhibited by the binding of 3-AT to the active center of catalase. Accordingly, 3-AT will be an interesting compound for investigation of the transport machinery of the peroxisomal tetrameric catalase.     

Synthesis and structural determination of three metal-organic frameworks in a Co-3-amino-1,2,4-triazole system

The hydrothermal reactions of cobalt(II) salts with 3-amine-1H-1,2,4-triazole (Hatrz) result in two kinds of coordination polymers, namely, 2D isoreticular layers based on a binuclear unit Co(atrz)Br (1) and Co(atrz)I (2), and 3D alternating layer architecture of Co₅(atrz)₇(N₃)₃ (3), which were structurally characterized by single-crystal X-ray diffraction techniques. Thermostabilities of all compounds were examined by thermogravimetric analysis. Isostructural compounds 1 and 2 display a two-dimensional layer structure where Co centers are linked by μ_1,2,4-atrz anions to form isoreticular layers containing sixteen-membered rings. Compound 3 is a 3D alternating layer architecture, which are based on parallel 1D chains and bimetal unit [N₃Co-(μ_1,4-atrz)-CoN₃]. The thermogravimetric analysis results of compounds 3 show that tremendous heat is released from its thermal decomposition, which indicates that the compound qualifies as a high-energy candidate.     

Transport of the herbicide 3-amino-1,2,4-triazole by cultured tobacco cells and leaf protoplasts

Transport of the herbicide amitrole (3-amino-1,2,4-triazole) by suspension cultured cells and leaf protoplasts of Nicotiana tabacum cv. Wisconsin 38 has been investigated. Cells were batch-cultured and routinely assayed 3 days after subculturing. Uptake rate was pH-independent, energy independent, and culture growth phase-dependent, with growing cells exhibiting the highest rates. At a concentration of 0.2 millimolar amitrole, uptake rates yielded a Q(10) of 1.6 in the 18 to 28 degrees C temperature range. Amitrole was not concentrated over a 48-hour period and showed unsaturable kinetics over the concentration range of 0.01 to 50.0 millimolar. Uptake was not significantly influenced by a 100-fold higher concentration of several amino acids (l-Asp, gamma-amino-n-butyric acid, l-His, l-Leu, l-Met, l-Trp), sucrose, glucose, fructose, and oxaloacetic acid. Uptake rate inhibition by malic acid and stimulation by NH(4)SCN were statistically significant. Amitrole was bound to cellular material, but uptake of amitrole by tobacco leaf protoplasts demonstrated that cell walls did not qualitatively influence uptake. These results indicate that amitrole enters the cells via simple diffusion.     

3,4-Disubstituted-5-mercapto-1,2,4-triazoles and Related Compounds

3,4-Diaryl-5-mercapto-1,2,4-triazoles have been prepared by the cyclization of the corresponding 1-aroyl-4-Substituted thiosemicarbazide with alkali. The resulting mercapto triazoles were converted into 3,4-disubstituted-5-alkylthio-1,2,4-triazoles with the action of different alkyl halides and some of the sulphides were converted into sulphones by oxidation with aqueous potassium permanganate.     

Characterization of oleate-nonutilizing mutants of Aspergillus nidulans isolated by the 3-amino-1,2,4-triazole positive selection method

Conidia of Aspergillus nidulans were mutagenized with ultraviolet light and were incubated on a special selective medium containing the catalase inhibitor 3-amino-1,2,4-triazole. From approximately 5 × 10⁷  viable UV-irradiated conidia tested, 423 stable mutants resistant to 3-amino-1,2,4-triazole were recovered, of which 40 were unable to grow on minimal medium with oleic acid as the sole carbon source. These oleate-nonutilizing (Ole^–) mutants did not grow on medium with carbon sources requiring functional peroxisomes (oleate, butyrate, acetate, or ethanol), but grew well on medium with carbon sources supposedly not requiring such organelles (glucose, glycerol, l-glutamate, or l-proline). The Ole^– mutants carried mutations in one of five nuclear genes affecting acetate utilization: acuJ, acuH, acuE, acuL, and perA. The perA21 strain (DL21) carried a mutation in a gene that is not allelic with any of the known acu loci and displayed a phenotype resembling that described in the Pim^– (peroxisome import defective) mutants of Hansenula polymorpha. Hyphae of the perA21 mutant contained a few small peroxisomes with the bulk of peroxisomal enzymes remaining in the 20,000 ×g supernatant, but produced wild-type levels of penicillin. Received: 16 April 1997 / Accepted: 26 July 1997