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At least 37 records · Page 2Linked to original sources
PubMed1985

Activity of titanocene dihalides against a human colon carcinoma heterotransplanted to athymic mice.

The antitumor activity of cis-diamminedichloroplatinum (II) and of two metallocene derivatives, titanocene dichloride (C5H5)2TiCl2 and titanocene dibromide (C5H5)2TiBr2, was investigated against a human colon adenocarcinoma heterotransplanted to athymic mice. The substances were administered at various doses on a Q2DX5 or a Q3DX5 schedule. Whereas cis-diamminedichloroplatinum (II) induced an only marginal tumor-inhibiting effect, both titanocenes markedly suppressed tumor development (T/C values: 23-40%) and caused stagnation and relative decrease of tumor growth, when they were applied in subtoxic doses far below the LD10 level. The results are remarkable with respect to the general insensitivity of human colorectal carcinomas to cytostatic agents.

Adenocarcinoma↗
PubMed1988

Planar chromatographic separation of enantiomers and diastereomers with cyclodextrin mobile phase additives.

A variety of racemic compounds were resolved using reversed-phase thin-layer chromatography (TLC) with mobile phases containing highly concentration solutions of beta-cyclodextrin (beta-CD). These include the drugs labetalol and mephenytoin, metallocenes, crown ethers, methyl-p-toluenesulfinate, nornicotine derivaties and several dansyl and beta-naphthylamide substituted amino acids. It was possible to resolve some racemates that could not be separated on beta-CD bonded phase liquid chromatography (LC) columns with this technique. Likewise there were some compounds that could be resolved with the LC approach that failed to separate with the present TLC method. In cases of racemates that could be resolved by either approach, it was found that the retention order was exactly opposite for the two methods. Enantiomeric resolution is highly dependent on mobile phase composition. In particular, the type and amount of organic modifier as well as the concentration of beta-CD affect the observed resolution. Possible reasons for the chromatographic behavior are discussed. Several diastereoisomeric compounds were separated as well, including steroid epimers and pharmaceutical compounds.

Amino Acids↗
PubMed1988

Photosubstitution of cymantrenylalanine as a tool in peptide chemistry. Synthesis and biological activity of new GnRH analogs.

Beyond its aromatic character and important hydrophobicity, cymantrenylalanine, a metallocenic amino-acid, can be easily photosubstituted with phosphine and phosphite ligands to readily yield new analogs with different hydrophobicity and steric hindrance. The incorporation of phosphine and phosphite ligands is described. As an illustration of the offered possibilities, the synthesis and the biological activity of two new GnRH analogs modified in position 6 are reported.

Alanine↗
PubMed1979

[Molybdocene dichloride as an antitumor agent (author's transl)].

The antitumor activity of molybdocene dichloride is tested against Ehrlich ascites tumor in CF1 mice. The application of 75 of 100 mg/kg 24 h after transplantation achieves 100% tumor inhibition until day 30. Following the d0 and d1 metallocene dichlorides of titanium and vanadium, molybdocene dichloride is the first analogous d2 system revealing similar antineoplastic properties.

Animals↗
PubMed1988

Anti-cancer action of metal complexes: electron transfer and oxidative stress?

Evidence is presented in support of an electron transfer mechanism for various metal complexes possessing anti-neoplastic properties. Cyclic voltammetry was performed on several metallocenes, bis(acetato)bis(imidazole)Cu(II), and coordination compounds (Cu or Fe) of the antitumor agents, bipyridine, phenanthroline, hydroxyurea, diethyldithiocarbamate, and alpha, alpha'-bis(8-hydroxyquinolin-7-yl)-4-methoxytoluene. The favorable reduction potentials ranged from +0.5 to -0.5 Electrochemical behavior is correlated in some cases with structure and physiological activity. Relevant literature data are discussed.

Antineoplastic Agents↗
PubMed1990

A selected ion monitoring method for quantifying simvastatin and its acid form in human plasma, using the ferroceneboronate derivative.

Simvastatin, a pro-drug lactone, forms the open carboxylic acid as a major metabolite that inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Simvastatin and the acid in plasma were quantified by a gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) method. These drugs were separated by solid-phase extraction and independently converted into a 1,3-diol-type compound. This compound reacted with ferroceneboronic acid to yield the cyclic boronate that gave satisfactory mass spectra for GC/MS/SIM measurements. The serum was dominated by the molecular ion appearing as the base peak, thereby leading to a sensitive and selective assay. The calibration curves for simvastatin and the acid were linear in their concentration range of 0.1-10 ng ml-1, where the values of coefficient of variation for both drugs were below 8%, except for the value of 11% for simvastatin at a concentration of 0.1 ng ml-1. The quantification limit for both drugs was 0.1 ng ml-1 on the basis of a signal-to-noise ratio of 4:1.

Ferrous Compounds↗
PubMed1992

Protection of guinea pigs against soman poisoning with ferrocene carbamate.

The protective effect of ferrocene carbamate pretreatment against soman poisoning was studied in guinea pigs. At doses corresponding to 1/20 x and 1/10 x LD50 of this carbamate a 20% and 45% decrease of the acetylcholinesterase in blood and brain, respectively, was obtained. In combination with additional pretreatment, diazepam, and therapy, HI-6 and atropine, the protective ratios (LD50 of soman in treated animals/LD50 of soman in untreated animals) were around 20 and 40, respectively. Animals pretreated with the high dose of the ferrocene carbamate that survived 10 x and 15 x LD50s of soman showed no remaining signs of poisoning after 24 h. Thus, the ferrocene carbamate afforded a better protection against soman than physostigmine. The explanation for this could be due to the properties of the ferrocene carbamate, not correlated to its cholinesterase inhibiting activity. This hypothesis is discussed.

Animals↗
PubMed1986

An animal model of iron overload and its application to study hepatic ferritin iron mobilization by chelators.

Administration of 3,5,5-trimethylhexanoyl ferrocene in the diet of male Wistar rats results in a substantial increase in hepatic ferritin protein (greater than 2-fold) and of ferritin iron (4-8-fold). The iron-loading in liver, under the conditions used, appears to be essentially in parenchymal cells rather than in reticulo-endothelial cells. It is suggested that the model represents a useful system for the study of the potential efficacy of new iron chelators for the mobilization of hepatic storage iron. The ability of desferal (DFO) and of a new siderophore, desferrithiocin (DFT), to mobilize hepatic ferritin iron is observed in this model of iron overload. Desferrithiocin stimulates ferritin iron mobilization, when administered either by gavage or by intraperitoneal injection, whereas desferal is active intraperitoneally but inactive orally. Our studies lead to the conclusion that DFT merits further examinations, for its activity as an orally active iron chelator.

Administration, Oral↗
PubMed1992

Studies of in vivo iron mobilization by chelators in the ferrocene-loaded rat.

The oral efficacy of the oral iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (CP20), 1,2-diethyl-3-hydroxypyrid-4-one (CP94) and desferrioxamine B (DFO) has been compared with intraperitoneal DFO in an experimental model of iron overload with similar biochemical and biophysical characteristics to those observed for human genetic haemochromatosis. The hepatic iron stores in the ferrocene-loaded rat were relatively stable and did not decrease at the end of the loading period. In contrast, the iron dextran rat model showed a rapid depletion of its iron stores 2 weeks after cessation of intraperitoneal injection. When CP20 and CP94 were administered to the ferrocene-loaded rat model in combination with an iron-free diet there were significant decreases in (i) total homogenate iron and (ii) hepatic ferritin iron when compared to the iron-loaded rat receiving the iron-free diet alone. Desferrioxamine, when administered by gavage, only showed chelation of ferritin iron, while intraperitoneal injection of desferrioxamine showed significant depletion of iron both in the total homogenate and ferritin. Subcellular fractionation of the hepatic organelle clearly showed that where there was depletion of homogenate iron there was a net decrease in the lysosomal fraction, while changes in ferritin iron were reflected by decreases in the cytosolic iron content. Although no assessment of net iron excretion was made, we suggest that the use of this animal model should ascertain the site of chelation by iron chelators.

Animals↗
PubMed1992

Electrochemical enzyme immunoassay for detection of toxic substances.

Sensors that provide reliable, rapid measurement of toxic substances are needed to solve significant human health and safety problems. We developed a new biosensor design that combines the advantages of immunoassay with electrochemical response. We established that this enzyme-linked immunosensor measures toxic substances in biological samples. The biosensor consists of two major elements: (1) an electrical conducting layer having immobilized enzyme, polyclonal or monoclonal antibodies, and other necessary reagents, and (2) the electronic components used in the signal readout. The result is an amperometric immunoassay based on coupling the immunochemical reaction to the enzyme electrode response by using a soluble, electrochemically active mediator. The specific question addressed was: Does the system's immunochemical detection reliably respond at sufficiently low analyte concentrations? We present our results in these areas: (1) enzyme immobilization on colloidal gold; (2) colloidal gold-enzyme deposition on the electrode surface; (3) mediator-antigen conjugate synthesis; (4) antibody incorporation at the electrode surface; (5) bioelectrode characterization and optimization; and (6) immunosensor demonstration to detect antigen. Sensors that employ immunochemical detection will have broad applicability to detect/diagnose toxic substances in biological samples such as blood and urine and in environmental samples such as wastewater and drinking water.

Biosensing Techniques↗
PubMed1986

Potentially-implantable, ferrocene-mediated glucose sensor.

We describe the construction and in vitro testing of a new potentially-implantable amperometric glucose sensor which is based on mediated electron transfer between immobilized glucose oxidase and a graphite base electrode. Under potentiostatic control, entrapped 1,1'-dimethylferrocene acts as an alternative electron acceptor to oxygen and provides a sensing strategy which is relatively unaffected by possible fluctuations in in vivo oxygen tension. Simple 1 mm wide electrodes with a polyurethane membrane gave linear current responses to at least 20 mmol/l glucose with a mean response time of 68 s. An acceptable proportion (17%) of electrodes had low or zero drift over 17 h at 37 degrees C. With plasma samples from diabetic and non-diabetic subjects, glucose concentrations measured by the sensor were significantly correlated with values obtained by a reference laboratory glucose analyser but were proportionally lower. Extension of this study to in vivo testing and further miniaturization of electrodes is justified.

Blood Glucose↗
PubMed1987

Toxicological evaluation of substituted dicyclopentadienyliron (ferrocene) compounds.

The acute toxicity of 3 substituted ferrocenes: acetylferrocene, ethylferrocene, and 2,2-bis(ethylferrocenyl)propane (Catocene) were studied in rats, rabbits and monkeys. Acetylferrocene was found to be the most toxic. The oral lethal dose was less than 5 mg/kg for female rats, between 5 and 50 mg/kg for male rats, and between 10 and 100 mg/kg for monkeys. The toxicity of acetylferrocene appeared to be delayed, with most mortality occurring on the third day after dosing. Acetylferrocene was also highly toxic by skin or eye exposure. Gross pathological examination revealed signs of pneumonopathy in both the rats and monkeys. The mechanism by which monkeys are less susceptible than rats to the toxicity of acetylferrocene is not clear.

Administration, Oral↗
PubMed1987

Sensitive ferrocene reagents for derivatization of thiol compounds in high-performance liquid chromatography with dual-electrode coulometric detection.

Three N-substituted maleimides possessing ferrocene as an electrophore were prepared and evaluated for pre-column derivatization of thiol compounds in high-performance liquid chromatography with dual-electrode coulometric detection. The utility of these reagents was investigated by employing N-acetyl-L-cysteine as a model compound. Among the three, N-(ferrocenyl) maleimide was the most favourable reagent with respect to reactivity, stability and electrochemical properties. The dual-electrode coulometric detection of the adduct showed high selectivity and sensitivity with a detection limit of 0.06 pmol. The proposed method is applicable to the determination of glutathione in biological specimens.

Adult↗
PubMed1988

[Ferrocene, ruthenocene and rhodocene analogs in haloperidol synthesis and organ distribution after labeling with 103Ru and 103mRh].

Ferrocene-Haloperidol was synthesized by N-alkylation of 4-(4'-chlorophenyl)- 4-hydroxypiperidine with 1-ferrocenyl-4-chlor-butan-1-on. By heating the ferrocene-haloperidol with 103RuCl3 the 103Ru-labelled ruthenocene-haloperidol was obtained. This compound showed a high affinity for lung but not for brain in rats and mice. The decay of the 103Ru labelled compound results in the formation of the 103mRh labelled rhodocene-haloperidol, which is rapidly oxidized by air to the corresponding rhodocinium-haloperidol. This compound can be separated by extraction and TLC.

Animals↗
PubMed1988

[Improved diagnosis using deuterated radiopharmaceuticals?--A comparison of the brain affinity of amphetamine analogs].

Ruthenocene amphetamine analogues have the same brain uptake as iodo-labelled amphetamines. This paper compares the organ-distribution of 103Ru labelled ruthenocene- or ferrocene-amphetamine analogues in mice and rats with the same amphetamine in which H-atoms were partly substituted by D-atoms. The uptake in the brain is increased up to 180-200% for deuterium substituted compounds. The pattern of excreted metabolites leads to the conclusion that the deuterated amphetamines are more slowly metabolised than normal (H) compounds.

Amphetamine↗
PubMed1991

An approach to the use of stable isotopes for DNA sequencing.

The sequencing of DNA by current procedures involves the use of radioisotopic or fluorescent labels. We propose that stable isotopes can be used as such labels and that the large number of stable isotopes available would allow multiplexing so that many DNA segments could be sequenced simultaneously. We have developed methods to use 57Fe2O3 to synthesize ferrocene and to attach the ferrocene to the 5' end of oligonucleotides. The 57Fe-labeled M13 universal primer functioned normally in a Sanger sequencing procedure. When a 57Fe-labeled oligonucleotide had migrated on a polyacrylamide gel it was readily located on the dried gel by scanning with resonance ionization spectroscopy (RIS) coupled with mass spectrometry. Using a 57Fe-labeled primer in a PCR reaction a 2000-bp DNA was produced that was detected by RIS on nylon membrane after agarose electrophoresis. The rapid analysis features of RIS coupled with the multispectral multiplexing possibilities of stable isotopes should significantly increase the rate of determination of DNA sequences.

Base Sequence↗
PubMed1992

Mediated amperometric determination of xylose and glucose with an immobilized aldose dehydrogenase electrode.

An enzyme electrode was constructed for amperometric determination of xylose and glucose. The electrode is based on the PQQ-dependent membrane-bound aldose dehydrogenase (ALDH) from Gluconobacter oxydans. ALDH was covalently immobilized on a graphite electrode. Immobilized dimethylferrocene, soluble ferrocene carboxylic acid and phenazine methosulphate were used as electron transfer mediators. When xylose was measured electrochemically using an electrode modified with ALDH and dimethylferrocene, the linear measurement range extended to 100 mM. For glucose measurement the linear measurement range was about one-tenth of that for xylose. The electrode showed fairly good stability; 50% of the original electrode response was still obtained after 5 days of intermittent use. The effect of possible leakage of adsorbed mediator was determined by measuring the response of an electrode with soluble mediator as a function of time. The reproducibility of the electrode was good, the standard deviation of the electrode response in ten measurements with the same electrode being only 2.7%.

Biosensing Techniques↗