Quinolin-2(1H)-one-triazole derived Schiff bases and their Cu(II) and Zn(II) complexes: Possible new therapeutic agents

The condensation of 4-amino-1,2,4-triazole with N-substituted-3-formyl-4-hydroxyquinolin-2-(1H)-one derivatives has lead to the synthesis of a new series of quinolin-2(1H)-one-triazole derived Schiff base ligands (1–3). Cu(II) and Zn(II) complexes (1a–3a and 1b–3b, respectively) of these ligands were also prepared. The complexes were characterised by standard techniques and for two of the complexes X-ray crystallography confirmed that the geometry at the metal centre was octahedral in both cases and that the Schiff base acted as a bidentate ligand coordinating to the metal(II) ion through the deprotonated oxygen and azomethine nitrogen atoms. All of the compounds were investigated for their antimicrobial activities against a fungal strain, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to be active against C. albicans but inactive against Staphylococcusaureus and Escherichia coli.     

Inhibition of <em>Burkholderia multivorans</em> Adhesion to Lung Epithelial Cells by Bivalent Lactosides

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in cystic fibrosis patients which is inherently resistant to antimicrobial agents. The mechanisms of attachment and pathogenesis of Bcc, a group of 17 species, are poorly understood. The most commonly identified Bcc species in newly colonised patients, Burkholderia multivorans, continues to be acquired from the environment. Development of therapies which can prevent or reduce the risk of colonization on exposure to Bcc in the environment would be a better alternative to antimicrobial agents. Previously, it has been shown that Bcc strains bound to many glycolipid receptors on lung epithelia. Using a real-time PCR method to quantify the levels of binding of B. multivorans to the lung epithelial cells, we have examined glycoconjugate derivatives for their potential to inhibit host cell attachment. Bivalent lactosides previously shown to inhibit galectin binding significantly reduced the attachment of B. multivorans to CF lung epithelial cells at micromolar concentrations. This was in contrast to monosaccharides and lactose, which were only effective in the millimolar range. Development of glycoconjugate therapies such as these, which inhibit attachment to lung epithelial cells, represent an alternative means of preventing infection with inherently antimicrobially resistant pathogens such as B. multivorans.     

The characterisation of selected antidepressant drugs using electrospray ionisation with ion trap mass spectrometry and with quadrupole time-of-flight mass spectrometry and their determination by high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry

The electrospray ionisation ion trap tandem mass spectrometry (ESI-MS(n)) of selected antidepressant drugs, i.e., citalopram, fluoxetine, mirtazapine, paroxetine, sertraline, and venlafaxine, has been investigated. Sequential product ion fragmentation experiments (MS(n)) have been performed in order to elucidate the degradation pathways for the [M+H](+) ions and their predominant product ions. These MS(n) experiments show certain characteristic fragmentations in that functional groups are generally cleaved from the ring systems as molecules such as H(2)O, amines and phenols. When an aromatic entity is present in a drug molecule together with a nitrogen-containing saturated ring structure as with mirtazapine, fragmentation initially occurs at the latter ring with the former being predictably resistant to fragmentation. Also, when an amine-containing drug molecule such as fluoxetine also contains a functional group, which liberates a phenol with a significantly lower DeltaH(f) (0) value than that of the corresponding amine, the phenol is preferentially liberated. The structures of product ions proposed for ESI-MS(n) can be supported by electrospray ionisation quadrupole-time-of-flight tandem mass spectrometry (ESI-QToF-MS/MS). These molecules can be identified and determined in mixtures at low ng/mL concentrations by the application of high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry (HPLC/ESI-MS(2)), which can also be used for their analysis in hair samples.     

Entropy as a Measure of Stability in a Manpower System

It is important when studying a manpower system to be able to measure stability of the experience distribution and thus evade possible trauma. This paper develops the use of entropy as such a measure, both for the comparison of different companies in steady state, and as a means of monitoring the changes in tenure distribution in time for a particular firm. It is shown for several companies that the entropy measure does in fact reflect the changes in length of service structure taking place within the firm.     

Modelling heterogeneity in a manpower system: a review

Manpower planning is an essential methodology for business and industry; it allows managers to make more efficient use of human resources. However, human behaviour is highly variable and it is therefore essential for manpower planning that population heterogeneity is successfully modelled. In this paper we review methods of incorporating population heterogeneity into manpower modelling. The analysis of differentials in a manpower system is emphasized since they are a source of aggregation error in stochastic models. Two strategies have been stressed, the use of observable sources of heterogeneity as they affect wastage, and the latent sources which cannot be identified precisely but are known to affect the key parameters of most models. Copyright © 2000 John Wiley & Sons, Ltd.     

Depletion kinetics of low-lying states of tungsten in the presence of NO,N2O,and SO2

The gas-phase reactivities of W(a⁵D_J, a⁷S₃) with N₂O, SO₂, and NO in the temperature range of 295–573 K are reported. Tungsten atoms produced by the photodissociation of W(CO)₆. The tungsten atoms were detected by a laser-induced fluorescence technique. The removal rate constants for the 6s²5d⁴ a⁵D_l states were found to be pressure dependent for all of the reactants. Removal rate constants for the 6s¹5d⁵ a⁷S₃ state were found to be fast compared to the a⁵D_J states and often approached the gas kinetic rate constant. The reaction rates for all the states were found to be pressure independent with respect to the total pressure. Results are discussed in terms of the different electronic configurations of the states of tungsten © 1997 John Wiley & Sons, Inc. Int J Chem Kinet 29: 367–375 1997     

A study of the analytical behaviour of selected psycho-active drugs using liquid chromatography, ion trap mass spectrometry, gas chromatography and polarography and the construction of an appropriate database for drug characterisation

This paper provides analytical chemical information on a range of psycho-active drugs. This analytical chemical information on liquid chromatography-electrospray ionisation-mass spectrometry (HPLC-ESI-MS), ion trap mass spectrometry (ESI-MSⁿ), gas chromatography-flame ionisation detection (GLC-FID) and polarographic behaviour is then incorporated into a database which is of use in drug characterisation. Application is found in the determination of selected drug compounds in hair samples.     

Bis-phenanthroline copper(II) phthalate complexes are potent in vitro antitumour agents with 'self-activating' metallo-nuclease and DNA binding properties

Three, structurally characterised, bis-phen Cu(II) complexes of the phthalate isomers display rapid, low micromolar in vitro cytotoxicity against a range of epithelial tumour cells. The complexes induce relaxation of supercoiled plasmid DNA in the absence of external reducing agents and display efficient CT-DNA, Poly[d(A-T)](2) and Poly[d(G-C)](2) binding.     

Biological activity and coordination modes of copper(II) complexes of Schiff base-derived coumarin ligands

The coordination modes of copper(II) complexes of Schiff base-derived coumarin ligands, which had previously shown good anti-Candida activity, were investigated by pH-potentiometric and UV-Vis spectroscopic methods. These studies confirmed the coordination mode of the ligands to be through the N of the imine and deprotonated phenol of the coumarin-derived ligand in solution. In addition, the more active complexes and their corresponding ligands were investigated in the presence of copper(II) in liquid and frozen solution by ESR spectroscopic methods. A series of secondary amine derivatives of the Schiff base ligands, were isolated with good solubility characteristics but showed little anti-Candida activity. However, cytotoxicity studies of the secondary amines, together with the copper complexes and their corresponding ligands, against human colon cancer and human breast cancer cells identified the chemotherapeutic potential of these new ligands.     

On the Moments and the Distribution of the Cost of a Semi Markov Model for Healthcare Systems

In this paper we extend our previous semi-Markov reward model which attached costs to duration in states, by including costs of making a transition from one state to another. Theoretical results concerning the moments and consequently the distribution of interval costs for every member and of the total cost per unit period at any time and also through time intervals are obtained and provided in analytic form for the semi Markov reward model with discounting. The results are applied to an open healthcare system. In the healthcare domain such transition costs allow us to evaluate the overall costs of therapy or clinical intervention where an operation or other treatment may be an option. This model can be used for strategic approaches to planning and evaluating long-term patient care. The results demonstrate the potential of the model to demonstrate differential costs of different therapeutic strategies and explore optimal solutions.