Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative

Xenobiotica ◽  
1992 ◽  
Vol 22 (1) ◽  
pp. 1-11 ◽  
Author(s):  
D. D. Stiff ◽  
J. T. Robicheau ◽  
M. A. Zemaitis
Keyword(s):  
Anticonvulsant Agent ◽  
Reductive Metabolism

scholarly journals Nitroaromatic Antibiotics as Nitrogen Oxide Sources

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 267
Author(s):  
Allison M. Rice ◽  
Yueming Long ◽  
S. Bruce King
Keyword(s):  
Nitric Oxide ◽  
Nitrogen Oxide ◽  
Reactive Nitrogen Species ◽  
Human African Trypanosomiasis ◽  
Anaerobic Bacteria ◽  
Mechanisms Of Action ◽  
Disease Treatment ◽  
Therapeutic Development ◽  
New Treatments ◽  
Reductive Metabolism

Nitroaromatic antibiotics show activity against anaerobic bacteria and parasites, finding use in the treatment of Heliobacter pylori infections, tuberculosis, trichomoniasis, human African trypanosomiasis, Chagas disease and leishmaniasis. Despite this activity and a clear need for the development of new treatments for these conditions, the associated toxicity and lack of clear mechanisms of action have limited their therapeutic development. Nitroaromatic antibiotics require reductive bioactivation for activity and this reductive metabolism can convert the nitro group to nitric oxide (NO) or a related reactive nitrogen species (RNS). As nitric oxide plays important roles in the defensive immune response to bacterial infection through both signaling and redox-mediated pathways, defining controlled NO generation pathways from these antibiotics would allow the design of new therapeutics. This review focuses on the release of nitrogen oxide species from various nitroaromatic antibiotics to portend the increased ability for these compounds to positively impact infectious disease treatment.

scholarly journals Reductive metabolism increases the proinflammatory activity of aldehyde phospholipids

2011 ◽  
Vol 52 (12) ◽  
pp. 2209-2225 ◽  
Author(s):  
Elena Vladykovskaya ◽  
Evgeny Ozhegov ◽  
J. David Hoetker ◽  
Zhengzhi Xie ◽  
Yonis Ahmed ◽  
...  
Keyword(s):  
Proinflammatory Activity ◽  
Reductive Metabolism

Immunosuppression by phenytoin: implication for altered immune competence in brain-tumor patients

1984 ◽  
Vol 61 (6) ◽  
pp. 1085-1090 ◽  
Author(s):  
Kenji Kikuchi ◽  
Christopher I. McCormick ◽  
Edward A. Neuwelt
Keyword(s):  
Brain Tumor ◽  
Culture Medium ◽  
Thymidine Incorporation ◽  
Pokeweed Mitogen ◽  
Immune Competence ◽  
Lymphocyte Function ◽  
Tumor Patients ◽  
Content Type ◽  
Anticonvulsant Agent

✓ This investigation was conducted to examine the immunosuppressive potential of phenytoin in vivo and to document a correlation between phenytoin therapy and depressed lymphocyte responsiveness to mitogens. It was thought that phenytoin, the most widely used anticonvulsant agent, may play some role in the immunosuppression seen in brain-tumor patients. The effect of phenytoin on mitogen-stimulated lymphocyte function was evaluated by tritiated (3H)-thymidine incorporation and lymphocyte nuclear size distribution. Lymphocytes from either phenytoin-treated or normal rabbits were incubated for 90 hours in culture medium in the presence of three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). Significant suppression of mitogen-induced activation of the lymphocytes from treated animals was demonstrated. The present studies suggest a possible connection between phenytoin therapy and altered immune competence in brain-tumor patients.

Reductive Activation of Carbon Tetrachloride by Human Haemoglobin

1993 ◽  
Vol 21 (1) ◽  
pp. 57-64
Author(s):  
Roberta Ferrara ◽  
Michela Rezzadore ◽  
Stefano Cazzaro ◽  
Roberto Tolando ◽  
Maurizio Manno
Keyword(s):  
Carbon Monoxide ◽  
Carbon Tetrachloride ◽  
Anaerobic Incubation ◽  
Reductive Activation ◽  
Anaerobic Conditions ◽  
Prosthetic Group ◽  
Experimental Conditions ◽  
Human Haemoglobin ◽  
Reductive Metabolism

The reductive metabolism of carbon tetrachloride (CC14) by human haemoglobin (Hb) was observed in vitro by absolute absorption spectra recorded under anaerobic conditions. The following results were obtained: 1) a decrease of the 430nm peak typical of free reduced Hb (Hb2+); 2) the formation of a shoulder of absorbance, attributable to the production of a complex between Hb2+ and a metabolite of CC14 carbon monoxide (Hb-CO); and 3) the oxidation of some Hb2+ to methaemoglobin (Hb3+). The concentration of these three forms — Hb2+, Hb-CO and Hb3+ — during anaerobic incubation of Hb with CC14 was calculated algebraically from the absolute spectra. CO production was then calculated from the concentration of Hb-CO, using a suitable calibration curve. Interestingly, under identical experimental conditions, a substrate-dependent loss of Hb-derived haem, but not of Hb itself nor of haem-derived porphyrin fluorescence, was measured. Preliminary HPLC studies to clarify the discrepancy and, in particular, the role and fate of the haem group, showed two substrate-dependent modified haem products. The results indicate that human Hb is able to catalyse the reductive activation of CCl4, and suggest that, during the process, its prosthetic group haem may be modified by CC14 metabolites to products which maintain a tetrapyrrolic structure but are unable to react with pyridine.

scholarly journals Crystal structure of creatininium 5-(2,4-dinitrophenyl)-1,3-dimethylbarbiturate monohydrate: a potential anticonvulsant agent

2016 ◽  
Vol 72 (5) ◽  
pp. 620-623
Author(s):  
Ponnusamy Poornima Devi ◽  
Doraisamyraja Kalaivani
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Water Molecule ◽  
Three Dimensional ◽  
Pyrimidine Ring ◽  
Membered Ring ◽  
Anticonvulsant Agent ◽  
The Mean ◽  
Anions And Cations ◽  
Molecular Salt

In the anion of the title hydrated molecular salt, C4H8N3O+·C12H9N4O7−·H2O [systematic name: 2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-3-ium 5-(2,4-dinitrophenyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate monohydrate], the 2,4-dinitrophenyl ring is inclined to the mean plane of the pyrimidine ring [r.m.s. deviation = 0.37 Å] by 43.24 (8)°. The five-membered ring of the creatininium cation (2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-3-ium) is essentially planar with an r.m.s. deviation of 0.015 Å. In the crystal, the anions and cations are linkedviaN—H...O hydrogen bonds, forming sheets parallel to theabplane. The sheets are linkedviaO—H...O hydrogen bonds involving the water molecule, forming a three-dimensional framework. Within the framework, there are C—H...O hydrogen bonds present. The title molecular salt displays anticonvulsant and hypnotic activities.

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