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At least 199 records · Page 11Linked to original sources
PubMed1999

Domain-structured N1,N2-derivatized hydrazines as inhibitors of ribonucleoside diphosphate reductase: redox-cycling considerations.

Eight analogues of 1-[5-halogenosalicylidene]-2-[2'-pyridinoyl]hydrazine and -[2'-pyridyl]hydrazine, four of 1-[pyridoxylidene]-2-[2'-pyridinoyl]hydrazine, seven of 1-[pyridoxylidene]-2-[2'-pyridyl]hydrazine, and one each of 1, 2-bis[pyridoxylidene]diaminoethane and bis[pyridoxylidenehydrazino]phthalazine were synthesized. Their solutions in DMF were assayed for activity against the metalloenzyme ribonucleoside diphosphate reductase (RdR), prepared from a subcutaneously growing murine tumor (sarcoma 180) implanted in B6D2F3 male mice. The 14C-labeled CDP reductase was assayed by the modified method of Takeda and Weber, in which [14C]cytidine was separated from deoxycytidine by thin-layer chromatography (TLC) on cellulose foil. Distribution of radioactivity was assessed with an automatic TLC linear analyzer. Of the 31 compounds tested, 13 were essentially inactive, 7 were highly active against RdR, and the remaining 20 were slightly more active than hydroxyurea (used as a reference compound). The mechanism of inhibition is discussed in terms of three alternative pathways, initiated by sequestration of iron embedded in the R1 subunit of the metalloenzyme to form a C-centered chelate radical (via redox cycling). Alternatively, the latter could either reduce the tyrosyl radical or intercept radicals generated in the reduction process.

Animals↗
PubMed2003

Synthesis of 17-alpha-substituted estradiol-pyridin-2-yl hydrazine conjugates as effective ligands for labeling with Alberto's complex fac-[Re(OH2)3(CO)3]+ in water.

The development of (99m)Tc-estradiol radiopharmaceuticals would be advantageous for the detection of estrogen receptor-positive breast tumors. Estradiol derivatives conjugated to organometallic tricarbonyl-Tc(I) and related Re(I) complexes are capable of achieving high receptor binding affinity, but effective methods for synthesizing radiolabeled complexes in water are not available. Our interest in the synthesis of 2-hydrazinopyridines as ligands for Tc and Re led us to investigate Pd-catalyzed amination reactions of halo-pyridine substrates with di-tert-butyl hydrazodiformate. Both 2- and 4-substituted halo-pyridine substrates undergo C-N coupling with di-tert-butyl hydrazodiformate to produce Boc-protected pyridine hydrazine derivatives. Only highly electrophilic 3-pyridine halides were converted to the hydrazine. The Boc-protected 5-bromopyridin-2-yl hydrazine substrate 3 was prepared by regioselective substitution at the 2-position of 2,5-dibromopyridine. This bifunctional chelate was attached to ethynyl or vinyl groups at the 17alpha position of estradiol, using Sonogashira and Suzuki/Miyaura coupling reactions to synthesize 1 and 2 in high yields, respectively. Deprotection of 1 under acidic conditions provided the hydrazine hydrochloride salt 25. The 17alpha-estradiol-tricarbonylrhenium(I) complex 4 was synthesized by labeling 25 with fac-[Re(OH(2))(3)(CO)(3)](+) in aqueous ethanol. This complex exhibited excellent stability and high receptor binding affinity for the estrogen receptor, and it is a promising model for evaluation of the analogous Tc-99m complexes as diagnostic imaging agents for breast tumors.

Animals↗
PubMed2006

Theoretical modeling of the oxidation of hydrazine by iron(II) phthalocyanine in the gas phase. Influence of the metal character.

The hydrazine oxidation by iron(II) phthalocyanine (Fe(II)Pc) has been studied using an energy profile framework through quantum chemistry theoretical models calculated in the gas phase at the density functional theory B3LYP/LACVP(d) level. We applied two models of charge-transfer mechanisms previously reported (J. Phys. Chem. A 2005, 109, 1196) for the hydrazine oxidation mediated by Co(II)Pc. Model 1 consists of an alternated loss of one electron and one proton, involving anionic and neutral species. Model 2 considers an alternated loss of two electrons and two protons and includes anionic, neutral, and cationic species. Both applied models describe how the charge-transfer process occurs. In contrast with the obtained results for Co(II)Pc, we found that the hydrazine oxidation mediated by Fe(II)Pc is a fully through-bond charge-transfer mechanism. On the other hand, the use of different charge-transfer descriptors (spin density, electronic population, condensed Fukui function) showed a major contribution of the iron atom in comparison with the cobalt atom in the above-mentioned process. These results could explain the higher catalytic activity observed experimentally for Fe(II)Pc in comparison with Co(II)Pc. The applied theoretical models are a good starting point to rationalize the charge-transfer process of hydrazine oxidation mediated by Fe(II)Pc.

Ferrous Compounds↗
PubMed2002

Flow-injection electrogenerated chemiluminescence detection of hydrazine based on its in-situ electrochemical modification at a pre-anodized platinum electrode.

In this paper. it was found that the enhancing effect of hydrazine on the weak electrogenerated chemiluminescence (ECL) signal of the electrooxidation of luminol at a pre-anodized platinum electrode was stronger than that of hydrazine at a bare platinum electrode. Based on this finding and the combination of this finding with a flow-injection technique, a novel, sensitive and selective ECL method for hydrazine was developed. Under the optimum experimental conditions, the relative ECL intensity was linear with hydrazine concentration over the range 2.0 x 10(-8) - 5.0 x 10(-5) mol L(-1), with a detection limit of 6.0 x 10(-9) mol L(-1).

Electrodes↗
PubMed1993

Hydrazine and hydroxylamine as probes for O2-reduction site of mitochondrial cytochrome c oxidase.

Reactions of hydrazine and hydroxylamine with bovine heart cytochrome c oxidase in the fully reduced state were investigated under anaerobic conditions following the visible-Soret spectral change. Hydrazine gave a sharp band at 575 nm with 20% decrease in the alpha band at 603 nm, and hydroxylamine induced a 2 nm blue-shift for the alpha band without any clear splitting. The Soret band at 443 nm was decreased significantly in intensity, with the concomitant appearance of a shoulder with hydrazine or a peak with hydroxylamine, both near 430 nm. The dependence on pH of the affinity of these reagents for the enzyme indicates that only the deprotonated forms of these reagents bind to the enzyme, suggesting a highly hydrophobic environment of the haem ligand-biding site. These spectral changes were largely removed by addition of cyanide or CO. However, detailed analysis of these spectral changes indicates that hydrazine perturbs the shape of the spectral change induced by cyanide and hydroxylamine perturbs that induced by CO. These results suggest that these aldehyde reagents bind to haem a3 iron as well as to a second site which is most likely to be the formyl group on the haem periphery, and that these two sites bind these reagents anti-cooperatively with each other.

Animals↗
PubMed1999

Hydrazine-conjugated cellulose for adsorption of glycated proteins.

Glycated proteins and advanced glycation end-products are postulated to play an important role in the development of complications due to diabetes mellitus or renal failure. The purpose of this study was to assess the ability of hydrazine-conjugated cellulose to adsorb glycated albumin. The samples used for adsorption test were artificially glycated albumin or the serum from patients with diabetes mellitus. The hydrazine-conjugated cellulose adsorbed more than 20% of the albumin glycated artificially over 77 days. The serum concentrations of glycated albumin in patients with diabetes mellitus (39.6 +/- 2.5% (mean +/- SEM), n = 14) were not decreased by incubation with cellulose alone (postincubation level, 39.7 +/- 2.5%) whereas they were significantly (p < 0.0001) reduced to 38.0 +/- 2.4% after incubation with hydrazine-conjugated cellulose. There was a significant correlation (r = 0.75, p < 0.01) between the preincubation levels of glycated albumin and the degree of adsorption. The hydrazine-conjugated cellulose has a higher affinity for albumin with greater glycation.

Adsorption↗
PubMed2000

Pyridoxine therapy in a patient with severe hydrazine sulfate toxicity.

OBJECTIVE: To report hydrazine sulfate as a cause of severe encephalopathy and to report its response to high-dose pyridoxine therapy. DESIGN: Case report. SETTING: An adult six-bed medical/surgical intensive care unit of a general hospital. PATIENT: One patient who developed severe encephalopathy after hydrazine sulfate. INTERVENTION: 5 g i.v. pyridoxine. MEASUREMENTS AND MAIN RESULTS: After 180 mg/day for 2 wks followed by 360 mg/day of hydrazine sulfate ingestion, our patient suffered severe encephalopathy. He received mechanical ventilation with attendant supportive measures and high-dose pyridoxine. The patient's encephalopathy resolved 24 hrs after receiving pyridoxine. CONCLUSION: Severe encephalopathy could result from hydrazine sulfate toxicity. High-dose pyridoxine is an effective treatment to reverse this encephalopathy.

Antineoplastic Agents↗
PubMed1989

Investigation of lipid peroxidation induced by hydrazine compounds in vivo in the rat.

Phenylhydrazine caused lipid peroxidation in rats in vivo as detected by expiration of ethane but this was not due to lipid peroxidation in liver, as there was no associated MDA production in this tissue. Hydrazine did not cause either ethane expiration or MDA formation. Both hydrazine and phenylhydrazine caused a significant increase in propane expiration. Phenylhydrazine significantly decreased packed cell volume and haemoglobin levels but hydrazine had no effect on these parameters. These data indicate that the early toxicity of hydrazine does not involve peroxidation of lipids whereas phenylhydrazine causes lipid peroxidation possibly within the erythrocyte, perhaps by interaction with red cell haemoglobin.

Alkanes↗
PubMed1971

Prophage induction in lysogenic Escherichia coli with simple hydroxylamine and hydrazine compounds.

The prophage-inducing capability of hydroxylamine sulfate and 36 of its derivatives, and of hydrazine dihydrochloride and dihydrazine sulfate and 43 of their derivatives, was determined in Escherichia coli W1709 (lambda). Maximal nontoxic concentrations up to 1 mg/ml were tested. Hydroxylamine sulfate was active at 2.5 mug/ml and the following 17 derivatives were active at concentrations ranging up to 500 mug/ml: alpha-naphthylhydroxylamine, N-hydroxy-2-aminofluorene, oxamyl hydroxamic acid, O-carbamoyl hydroxylamine (isohydroxyurea), N-hydroxyurethane, N-methylhydroxylamine HCl, salicylhydroxamic acid, oxalohydroxamic acid, methoxyamine HCl, ethoxyamine HCl, N, N-diethylhydroxylamine oxalate, formaldoxime, formamidoxime, acetohydroxamic acid, acetaldoxime, acetone oxime, and hydroxyguanidine sulfate. Hydrazine dihydrochloride and dihydrazine sulfate were effective inducers at 5.0 and 2.5 mug/ml, respectively, and the following nine derivatives of them were active at concentrations ranging up to 500 mug/ml: phthalic acid hydrazide, phenylhydrazine HCl, p-nitrophenylhydrazine, p-chlorophenylhydrazine HCl, formylhydrazine, carbohydrazide, semicarbazide HCl, 1-methyl-1-phenyl-hydrazine sulfate, and acetic acid hydrazide. Nineteen hydroxylamine and 34 hydrazine derivatives were ineffective as inducers. Application of the prophage-induction system as a tool for detection of responsive hydroxylamino and hydrazino compounds which may be potential toxicological hazards in the environment is discussed.

Coliphages↗
PubMed1995

Occupational exposure to hydrazine and subsequent risk of cancer.

OBJECTIVES: The aim was to examine the cause specific mortality of men exposed to hydrazine. METHODS: Hydrazine was produced at a factory in the east midlands between 1945 and 1971. The cohort of all 427 men who were employed there for at least six months with varying degrees of occupational exposure to hydrazine were followed up until the end of January 1992. RESULTS: By the end of July 1982 49 deaths had occurred and the observed mortality was found to be close to that expected at each level of exposure. By the end of January 1992 a further 37 deaths had occurred. Again the observed mortality was close to that expected for all causes and also for lung cancer, cancers of the digestive system, other cancers, and all other causes, irrespective of the level of exposure. CONCLUSIONS: The results weigh against there having been any material hazard of occupational exposure to hydrazine. The small number of men studied means, however, that a relative risk as high as 3.5 for lung cancer cannot confidently be excluded.

Cause of Death↗
PubMed1994

Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer.

PURPOSE: Hydrazine sulfate is a controversial agent that was originally studied in cancer patients approximately 20 years ago. Based on a series of recent trials that suggested that this drug might have utility in cancer patients, we conducted this study. PATIENTS AND METHODS: Patients with metastatic colorectal cancer were randomized to receive hydrazine sulfate or placebo in a double-blinded manner. Protocol patients did not concurrently receive any other systemic antineoplastic treatment. RESULTS: There were 127 assessable patients entered onto this clinical trial. Data from the study showed trends both for poorer survival and for poorer quality of life (QL) in the hydrazine group. There were no significant differences in the two study arms with regard to anorexia or weight loss. CONCLUSION: This trial failed to demonstrate any benefit for hydrazine sulfate.

Aged↗
PubMed1994

Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer.

PURPOSE: Hydrazine sulfate, an agent that appears to inhibit gluconeogenesis, has been studied in cancer patients for approximately 20 years. There was a recent resurgence of interest in this drug when subset analysis of a small placebo-controlled, double-blind, clinical trial reported improved survival among non-small-cell lung cancer patients with a good performance status who were randomized to receive this drug along with standard chemotherapy. PATIENTS AND METHODS: Patients on this trial had newly diagnosed, unresectable non-small-cell lung cancer and were treated with cisplatin and etoposide. In addition, they were randomized to receive hydrazine sulfate or placebo in a double-blind manner. RESULTS: A total of 243 patients were randomized. Response rates were similar in the two treatment arms. There were trends for worse time to progression and survival in the hydrazine sulfate arm. No significant differences were noted in the two study arms with regard to toxicity or quality of life (QL). CONCLUSION: This trial failed to demonstrate any benefit for patients who received hydrazine sulfate.

Antineoplastic Agents↗
PubMed1993

Chemical modification of antitumor alkaloids, 20(S)-camptothecin and 7-ethylcamptothecin: reaction of the E-lactone ring portion with hydrazine hydrate.

The structure of the N-amino pyridone (4a) obtained by the reaction of camptothecin (1a) with hydrazine was determined by X-ray crystallography. A mixture of 7-ethylcamptothecin (1b) and hydrazine hydrate was stirred at room temperature, and the hydrazide (2b) was isolated as its diacetate 2c. Treatment of the 17-O-acetyl amide (5a) with hydrazine gave 1b (74% yield) and the N-amino lactam 6 (11% yield). Compounds with bulky acyl groups, 5c--e, gave 6 in modest yields. The N-amino lactam 6 was smoothly dehydrated into the pyridone 4d by refluxing in hydrazine hydrate.

Animals↗
PubMed2000

Fatal hepatorenal failure associated with hydrazine sulfate.

BACKGROUND: The Internet has revolutionized the manner in which patients obtain information about health care. This technology has also allowed patients to obtain directly both prescription and nonprescription therapies. OBJECTIVE: To report a case of fulminant hepatorenal failure associated with the use of hydrazine sulfate, an unregulated alternative remedy for cancer marketed on the Internet. DESIGN: Case report. SETTING: Academic medical center. PATIENT: A 55-year-old man with maxillary sinus cancer. INTERVENTION: Self-medication with hydrazine sulfate. MEASUREMENTS: Serum liver and renal function tests; histologic evaluation of liver and kidney tissue. RESULTS: The patient developed hepatic encephalopathy, renal failure, and profound coagulopathy. He died after severe gastrointestinal hemorrhage developed. Autopsy revealed autolysis of the kidneys and submassive bridging necrosis of the liver. CONCLUSION: Fatal hepatorenal failure may occur after the use of hydrazine sulfate. This fatal complication must be considered in anyone taking or contemplating the use of hydrazine sulfate.

Antineoplastic Agents↗
PubMedDate not supplied

A review of the natural occurrence, synthetic production and use of carcinogenic hydrazines and related chemicals.

This writing details the natural occurrence, synthetic production and use of the carcinogenic hydrazines and related chemicals. Twenty-three such chemicals were found in nature in mushrooms, tobacco, bay leaves, antibiotics, soil and other sources. The synthetically-produced hydrazines and related chemicals include 61 compounds which were or are in use as pharmaceutical drugs, agricultural substances, industrial chemicals and fuels for military and space vehicles and rockets. Because there is an overlap between the naturally-occurring and synthetically-produced compounds, their total number is 76. Altogether, 98 hydrazines and related chemicals were studied for carcinogenic action thus far, of which 84 were found to be carcinogenic and the remaining 14 were inactive. This means that the human population is exposed in various degrees to a substantial number of these agents. Therefore, the hydrazine class, unlike the polycyclic aromatic hydrocarbons, N-nitroso compounds, and aromatic amines, poses a greater environmental risk to the human population. In view of these considerations, it appears reasonable to proceed with additional experimentation in this field of interest.

Agrochemicals↗
PubMed1975

Synthetic and naturally occurring hydrazines as possible cancer causative agents.

The various synthetic substituted hydrazines, which cause tumors in animals, are briefly enumerated. To date, 19 of them have proved to be tumorigenic in animals. A number of these chemicals are found today in the environment, in industry, in agriculture, and in medicine, and the human population is exposed to a certain degree to some of them. Hydrazine also occurs in nature in tobacco and tobacco smoke. The three other naturally occurring hydrazine compounds are N-methyl-N-formylhydrazine, which occurs in the wild edible mushroom, Gyromitra esculenta, and beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine and 4-hydroxymethylphenylhydrazine, which are found in the commonly eaten cultivated mushroom, Agaricus bisporus. Tumorigenesis studies with the naturally occurring hydrazines are in progress.

Basidiomycota↗
PubMed2004

Syntheses and characterisation of N,N'-biscarbazolyl azine and N,N'-carbazolyl hydrazine derivatives and their antimicrobial studies.

Reaction of 1-oxo-1,2,3,4-tetrahydrocarbazoles 1a-e with hydrazine hydrate in absolute ethanol afforded N,N'-bis-carbazolylazine derivatives 2a-e. Treatment of compounds 1a-e with hydroxylamine hydrochloride in ethanol with a catalytic amount of pyridine resulted in the formation of 1-hydroxyimino-1,2,3,4-tetrahydrocarbazoles 3a-e. Reduction of 3 with hydrazine hydrate in the presence of palladized carbon afforded N,N'-carbazolyl hydrazine derivatives 4a-e. The newly formed compounds were characterized by IR, 1H NMR, mass spectra and by elemental analysis. All compounds proved to have great potentialities as antibacterial and antifungal agents due to the presence of the azine or the hydrazine group. Particularly, the chloro substituted derivatives 2e and 4e showed excellent antibacterial and antifungal activity.

Anti-Bacterial Agents↗
PubMed1986

The mechanism of inactivation of dopamine beta-hydroxylase by hydrazines.

Dopamine beta-hydroxylase is inactivated by phenyl-, phenethyl-, benzyl-, and methylhydrazine, but not by hydrazine itself. With phenyl-, methyl-, and phenethylhydrazine, the rate of inactivation decreases in the presence of ascorbate and increases in the presence of tyramine. Reduction of the enzyme-bound copper occurs with all of the hydrazines tested. In the presence of the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone the carbon-centered radicals generated from each compound are trapped. This is consistent with reduction of the enzyme-bound copper by the hydrazine-containing compounds, resulting in formation of the hydrazine cation radical. Homolytic cleavage of the carbon-nitrogen bond then generates a carbon-centered radical which reacts with the enzyme, resulting in inactivation. Inactivation with [14C]phenylhydrazine results in the incorporation of 0.94 molecule of label per enzyme subunit. Benzylhydrazine behaves as a mechanism-based inhibitor of the enzyme. Both benzyl- and phenethylhydrazine are substrates for dopamine beta-hydroxylase. The second-order rate constant for inactivation of dopamine beta-hydroxylase by benzylhydrazine in the presence of ascorbate is increased about 4-fold when the benzylic hydrogens are replaced with deuterium. The apparent Vmax shows an observed deuterium kinetic isotope effect of 13 +/- 2. The partition ratio for product formation versus inactivation is 11-fold less for alpha,alpha-d2-benzylhydrazine. These results are interpreted in terms of a model where inactivation is due to abstraction of an electron from nitrogen instead of abstraction of a hydrogen atom from the benzylic carbon.

Adrenal Medulla↗