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Fractionation of the bioactive dichloromethane extract from the aerial parts of Stachys glutinosa led to the isolation of four flavones, xanthomicrol (1), sideritoflavone (2), 8-methoxycirsilineol (3), and eupatilin (4), along with two neo-clerodane diterpenes, roseostachenone (8) and a new compound, 3α,4α-epoxyroseostachenol (7). In order to study structure-activity relationships, two methoxyflavones [5-demethyltangeretin (5) and tangeretin (6)] were synthesized by the methoxylation of xanthomicrol. The isolated compounds (1-4, 7, and 8) as well as the xanthomicrol semisynthetic derivatives (5 and 6) were evaluated for their binding affinity to the μ and δ opioid receptors. Xanthomicrol was the most potent binder to both μ and δ receptors, with a Ki value of 0.83 and 3.6 μM, respectively. Xanthomicrol administered intraperitoneally in mice at a dose of 80 mg/kg significantly reduced morphine-induced antinociception in the tail flick test. Our results suggested that xanthomicrol is a μ opioid receptor antagonist. Docking experiments were carried out to acquire a deeper understanding about important structural aspects of binding of xanthomicrol. In summary, these data suggest that xanthomicrol is a valuable structure for further development into a potential μ opioid receptor antagonist.

Several ligands can bind to the non-canonical G-quadruplex DNA structures thereby stabilizing them. These molecules can act as effective anticancer agents by stabilizing the telomeric regions of DNA or by regulating oncogene expression. In order to better interact with the quartets of G-quadruplex structures, G-binders are generally characterized by a large aromatic core involved in π-π stacking. Some natural flexible cyclic molecules from Traditional Chinese Medicine have shown high binding affinity with G-quadruplex, such as berbamine and many other alkaloids. Using the structural information available on G-quadruplex structures, we performed a high throughput in silico screening of commercially available alkaloid derivative databases by means of a structure-based approach based on docking and molecular dynamics simulations against the human telomeric sequence d[AG3(T2AG3)3] and the c-myc promoter structure. We identified 69 best hits reporting an improved theoretical binding affinity with respect to the active set. Among them, a berberine derivative, already known to remarkably inhibit telomerase activity, was related to a better theoretical affinity versus c-myc.

A small library of 1,3-diarylpropenones was designed and synthesized as dual inhibitors of both HIV-1 reverse transcriptase (RT) DNA polymerase (DP) and ribonuclease H (RNase H) associated functions. Compounds were assayed on these enzyme activities, which highlighted dual inhibition properties in the low-micromolar range. Interestingly, mutations in the non-nucleoside RT inhibitor binding pocket strongly affected RNase H inhibition by the propenone derivatives without decreasing their capacity to inhibit DP activity, which suggests long-range RT structural effects. Biochemical and computational studies indicated that the propenone derivatives bind two different interdependent allosteric pockets., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two new thienylheptatrienamides (1, 5) and one new neo-lignan (12), together with thirteen known compounds (2, 3, 4, 6-11, 13-16) were isolated from the roots of Otanthus maritimus. The structures of the new compounds were elucidated on the basis of extensive 1D and 2D NMR experiments as well as high resolution mass spectrometry. All the isolated amides (1-10), the known pontica epoxide (11) and the new neo-lignan (12) were evaluated for their binding affinity to the CB1 and CB2 as well as to the μ and δ opioid receptors. Some alkylamides showed moderately high binding affinity for CB2 receptors and 1-[(2E,4E,8Z)-tetradecatrienoyl]piperidine (10) resulted the most active one with a Ki value of 160 nM. As far as we know, this is the first example of a tertiary alkylamide that binds CB2 receptors with significant potency. Compounds that showed the highest affinity for cannabinoid receptors (6-8, 10) were much less potent against opioid receptors. Primary structure-activity relationship is discussed. Docking experiments were carried out with the aim to understand the key interactions of the most active compounds with CB2 receptor., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Nowadays, it has been demonstrated that DNA G-quadruplex arrangements are involved in cellular aging and cancer, thus boosting the discovery of selective binders for these DNA secondary structures. By taking advantage of available structural and biological information on these structures, we performed a high throughput in silico screening of commercially available molecules databases by merging ligand- and structure-based approaches by means of docking experiments. Compounds selected by the virtual screening procedure were then tested for their ability to interact with the human telomeric G-quadruplex folding by circular dichroism, fluorescence spectroscopy, and photodynamic techniques. Interestingly, our screening succeeded in retrieving a new promising scaffold for G-quadruplex binders characterized by a psoralen moiety.

The HIV-1 reverse transcriptase (RT) is one of the most attracting targets for the development of early phase infection inhibitors. Although many RT inhibitors have been approved for the treatment of HIV-1 infection, they all target the polymerase function of this enzyme. So far, no drugs are available for the inhibition of the RT associated ribonuclease H function (RNase H), which plays an essential role in the HIV replication cycle. Moreover it should be reported that many of the known RT inhibitors, targeting the polymerase function, enhance the RNase H activity, indicating that, although spatially distinct, a close relation occurs between the two functions. The aim of this review is to summarise the efforts in the design of new inhibitors either characterized by a novel mechanism of action or capable of blocking both RT associated functions, as well as pointing out the main binding features of the known RT inhibitors.

We report the first application of ligand-based virtual screening (VS) methods for discovering new compounds able to inhibit both human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT)-associated functions, DNA polymerase and ribonuclease H (RNase H) activities. The overall VS campaign consisted of two consecutive screening processes. In the first, the VS platform Rapid Overlay of Chemical Structures (ROCS) was used to perform in silico shape-based similarity screening on the NCI compounds database in which a hydrazone derivative, previously shown to inhibit the HIV-1 RT, was chosen. As a result, 34 hit molecules were selected and assayed on both RT-associated functions. In the second, the 4 most potent RT inhibitors identified were selected as queries for parallel VS performed by combining shape-based, 2D-fingerprint and 3D-pharmacophore VS methods. Overall, a set of molecules characterized by new different scaffolds were identified as novel inhibitors of both HIV-1 RT-associated activities in the low micromolar range., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Monoamine oxidase B (MAO-B) is a promising target for the treatment of neurodegenerative disorders. We report the synthesis and the biological evaluation of halogenated derivatives of 1-aryliden-2-(4-phenylthiazol-2-yl)hydrazines. The fluorinated series shows interesting activity and great selectivity toward the human recombinant MAO-B isoform expressed in baculovirus infected BTI insect cells. The multiple crystal structures alignment of the enzyme highlighted pronounced induced fit (IF) adaptations with respect to bound ligands. Therefore, IF docking (IFD) experiments and molecular dynamic (MD) simulations were carried out to reveal the putative binding mode and to explain the experimentally observed differences in the activity of 1-(aryliden-2-(4-(4-chlorophenyl)thiazol-2-yl)hydrazines. The importance of water molecules within the binding site was also investigated. These are known to play an important role in the binding site cavity and to mediate protein-ligand interactions. Detailed analyses of the trajectories provide insights on the chemical features required for the activity of this scaffold. In particular it was highlighted the importance of fluorine atom interacting with the water close to the cofactor and the influence of steric bulkiness of substituents in the arylidene moiety. Free energy perturbation (FEP) analysis confirmed experimental data. The information we deduced will help to develop novel high-affinity MAO-B inhibitors., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Among different heterocyclic chemotypes incorporating two nitrogen atoms, pyrazolines could be considered a valid pharmacophore for the synthesis of selective monoamine oxidase (MAO) inhibitors because they were developed by the cyclization of the early hydrazine derivatives such as isocarboxazid. Substituted pyrazolines, decorated with different functional groups, are important lead compounds endowed with a large amount of biological activities. As a matter of this, most of them were also evaluated as dual inhibitors with a synergistic action towards different classes of enzymes (ciclooxygenase, acetylcholinesterase, butyrylcholinesterase). Moreover due to the direct correlation with the recognized MAO inhibition, this scaffold displayed antidepressant and anticonvulsant properties in animal models.

3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles were designed, synthesized, and tested as inhibitors against human monoamine oxidase (MAO) A and B isoforms. Several compounds, obtained as racemates, were identified as selective MAO-B inhibitors. The enantiomers of some derivatives were separated by enantioselective HPLC and tested. The R-enantiomers always showed the highest activity. Docking study and molecular dynamic simulations demonstrated the putative binding mode. We conclude that these 1,3,4-oxadiazoles derivatives are promising reversible and selective MAO-B inhibitors.

Introduction: Vascular adhesion protein-1 (VAP-1)/semicarbazide-sensitive amine oxidase (SSAO) is an adhesion protein involved in leukocyte trafficking and inflammatory processes, with a special amine oxidase activity. Inhibitors have been mainly developed for treating chronic inflammatory disorders. The utility of inhibitors as antiangiogenic agents in ophthalmological and oncological diseases is currently under evaluation. SSAO substrates may mimic several insulin effects, although their utility for the treatment of diabetes is still far from being fully understood., Areas Covered: This paper reviews the patent literature of SSAO/VAP-1 inhibitors and substrates, for the period of 1990 - 2010. The current stage of SSAO/VAP-1-interacting agents published in patents is described, along with their chemical structures and pharmacological uses., Expert Opinion: SSAO/VAP-1 is a promising anti-inflammatory target. Another important field for therapeutic application of these inhibitors may be ophthalmology, due to their antiangiogenic effects. SSAO substrates might also be of therapeutic value in the treatment of diabetes; however, more extensive research has to be undertaken to validate this approach.

Some differently substituted 3-aryl-4,5-dihydropyrazoles-1-carbothioamides have been synthesised with the aim to investigate their monoamine oxidase inhibitory activity. The chemical structures of the compounds have been characterized by means of their IR, (1)H NMR, (13)C NMR spectroscopic data and elemental analyses. All the active compounds showed a selective activity towards the B isoform of the enzyme, regardless of the substitution on the heterocyclic ring. The inhibition of the enzymatic activity was measured on human recombinant MAO isoforms, expressed in baculovirus infected BTI insect cells. Docking experiments were carried out with the aim to rationalize the mechanism of inhibition of the most active and selective compound., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

A direct HPLC enantioseparation of three new chiral oxadiazoline derivatives endowed with potential MAO-B inhibitory activity was accomplished on the immobilised Chiralpak IA chiral stationary phase. Multi-mg amounts of enantiomers with high enantiomeric purity (ee> or =98%) were rapidly collected using pure dichloromethane as eluent. The absolute configuration and chiroptical properties of the enantiomers isolated at semipreparative scale were exhaustively determined., (Copyright 2010 Elsevier B.V. All rights reserved.)

G-Pisa is an experiment investigating the possibility of operating a high-sensitivity laser gyroscope with area less than 1 m2 for improving the performances of the mirrors suspensions of the gravitational wave antenna Virgo. The experimental set-up consists of a He-Ne ring laser with a 4-mirror square cavity. The laser is pumped by an RF discharge where the RF oscillator includes the laser plasma to reach a better stability. The contrast of the Sagnac fringes is typically above 50% and a stable regime has been reached with the laser operating in either single mode or multimode. The effect of hydrogen contamination on the laser was also checked. A low-frequency sensitivity, below 1 Hz, in the range of 10(-8)(rad/s)/square root(Hz) has been measured.

A direct semipreparative HPLC enantioseparation of two chiral thiazolidinone derivatives having cyclooxygenase-2 inhibition activity was performed on the Chiralpak IA chiral stationary phase. Semipreparative amounts of enantiopure forms were collected using acetonitrile-ethanol-trifluoroacetic acid mixtures as mobile phase. The absolute configuration of both compounds was unequivocally established by single-crystal X-ray diffraction method and correlated to the chiroptical properties of isolated enantiomers., (Copyright 2009 Wiley-Liss, Inc.)

Two series of 2,5-diaryl-1,3,4-oxadiazolines have been studied by multinuclear magnetic resonance and density functional theory calculations. A full NMR spectroscopic characterization has been performed and excellent remote Hammett correlations (sigma(p) or sigma(p)+) have been found for para substitution in the two aryl rings through at least 11 bonds, notwithstanding the presence in the path of atoms that should act as insulators and a lack of correlation for some of the intermediate atoms. The computational investigation on the electronic delocalization, performed with the ACID (anisotropy of the induced current density) method, reveals indeed that electrons are delocalized in almost the entire molecule despite the presence of the insulators., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Acetylation is a key modulator of genome accessibility through decondensation of the chromatin structure. The balance between acetylation and opposite deacetylation is, in fact, a prerequisite for several cell functions and differentiation. To find modulators of the histone acetyltransferase Gcn5p, we performed a phenotypic screening on a set of newly synthesized molecules derived from thiazole in budding yeast Saccharomyces cerevisiae. We selected compounds that induce growth inhibition in yeast strains deleted in genes encoding known histone acetyltransferases. A novel molecule CPTH2, cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl)hydrazone, was selected based on its inhibitory effect on the growth of a gcn5Delta strain. We demonstrated a specific chemical-genetic interaction between CPTH2 and HAT Gcn5p, indicating that CPTH2 inhibits the Gcn5p dependent functional network. CPTH2 inhibited an in vitro HAT reaction, which is reverted by increasing concentration of histone H3. In vivo, it decreased acetylation of bulk histone H3 at the specific H3-AcK14 site. On the whole, our results demonstrate that CPTH2 is a novel HAT inhibitor modulating Gcn5p network in vitro and in vivo.

Background: The combination of a proteasome inhibitor with a taxane has potential clinical synergism that prompted a clinical test., Patients and Methods: The maximum tolerated dose (MTD) and recommended dose (RD) of intravenous (i.v.) Bortezomib (B) (days 1, 4, 8, 11) and i.v. Paclitaxel (PTX) (days 1, 8) every 3 weeks was evaluated in patients with advanced solid tumours. The RD was tested in patients with breast, ovarian and prostate cancer. At the RD, microarray analysis of transcriptional profiles was carried out before and after the first dosing in peripheral blood mononuclear cells (PBMC)., Results: Thirty-one patients were enrolled and 22 were treated at the RD that corresponded to B 1.3mg/m(2) and PTX 100mg/m(2). The main toxicity was cumulative peripheral neuropathy (76% of patients; grade 3-4 in 9%) that required treatment discontinuation in six patients, followed by diarrhoea (55%) and fatigue (41%). Nine partial responses (30%) were observed (three breast cancer, four ovary, two prostate patients). Significant (p<0.05) and consistent changes (>70% of patients) in transcriptome were observed., Conclusions: The incidence of peripheral neuropathy and the anti-tumour activity comparable to that of single-agent PTX do not support further development of this regimen.

A series of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones have been investigated for their ability to inhibit selectively the activity of the human A and B isoforms of monoamine oxidase (MAO). The target compounds, which present a stereogenic center on the cyclohexane ring, were obtained as pure (R) and (S) enantiomers by enantioselective HPLC. The absolute configuration of homochiral forms isolated on a semipreparative scale was obtained by a combined strategy based on chemical correlation and single-crystal X-ray diffraction. All compounds showed higher activity against the human MAO-B isoform with IC50 values ranging between 26.81 +/- 2.74 microM and 14.20 +/- 0.26 nM, and the assays carried out on the pure enantiomers showed higher activity for the (R) form. A computational study was performed by molecular mechanics, DFT-based quantomechanics, and docking techniques on the most active and human MAO-B selective inhibitor 8.

SSAO/VAP-1 is not only involved in the metabolism of biogenic and xenobiotic primary amines and in the production of metabolites with cytotoxic effects or certain physiological actions, but also plays a role, for example, as an adhesion molecule, in leukocyte trafficking, in regulating glucose uptake and in adipocyte homeostasis. Interest in the enzyme has been stimulated by the findings that the activities of the SSAOs are altered (mostly increased) in various human disorders, including diabetes, congestive heart failure, liver cirrhosis, Alzheimer's disease and several inflammatory diseases, although the underlying causes are often unknown. On the basis of their insulin-mimicking effect, SSAO substrates are possibly capable of ameliorating metabolic changes in diabetes, while SSAO inhibitors (somewhat of a contradiction) are of potential benefit in preventing diabetes complications, atherosclerosis and oxidative stress contributing to several disorders or modulating inflammation, and hence may be of substantial therapeutic value. Great efforts have been made to develop novel compounds which may lead to future drugs useful in therapy, based on their effects on SSAO/VAP-1, and some of the results relating to novel substrates and inhibitors are surveyed in the present review.

In this paper, we report on the synthesis of a novel series of 2-thiazolylhydrazone derivatives and the influence of the substituents on the thiazole ring on antifungal activity. All synthesized compounds were screened for their in vitro activities against 22 clinical isolates of Candida spp., representing six different species, compared to clotrimazole as a reference compound. Some of the tested compounds were found to possess significant antifungal activity when compared to clotrimazole, in particular compound 14 which exhibited higher potency against most of the Candida spp. considered. The compounds that were most active as anti-Candida agents were also submitted to cytotoxic screening by the Trypan Blue dye exclusion assay and in general they were shown to induce low cytotoxic effects.

A series of 2-thiazolylhydrazone derivatives have been investigated for the ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO) selectively. All of the compounds showed high activity against both the MAO-A and the MAO-B isoforms with pKi values ranging between 5.92 and 8.14 for the MAO-A and between 4.69 and 9.09 for the MAO-B isoforms. Both the MAO-A and the MAO-B isoforms, deposited in the Protein Data Bank as model 2BXR and 1GOS, respectively, were considered in a computational study performed with docking techniques on the most active and MAO-B-selective inhibitor, 18.

The direct HPLC enantioseparation of five pairs of new chiral pyrazole derivatives on coated cellulose- and amylose-based chiral stationary phases (Chiralpak AD, Chiralcel OJ and Chiralcel OJ-RH) and new immobilised amylose-based Chiralpak IA CSP was performed. Very high enantioselectivity factor (alpha) values were achieved in polar organic and reversed-phase conditions by using OJ-RH as CSP. Chiralpak IA exhibited an excellent chiral resolving ability in normal-phase mode and it allowed the enantioseparation of analytes investigated with resolution factors (Rs) >20. Due to its bonded nature, it was successfully employed at analytical and semipreparative scale in combination with normal-phase eluents containing "non-standards" solvents such as acetone.

A novel series of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)-pyrazole derivatives have been synthesized and investigated for the ability to inhibit selectively the activity of the A and B isoforms of monoamine oxidase (MAO). All the synthesized compounds show high activity against both the MAO-A and the MAO-B isoforms with Ki values between 27 and 4 nM and between 50 and 1.5 nM, respectively, except for a few derivatives whose inhibitory activity against MAO-B was in the micromolar range. Knowing that stereochemistry may be an important modulator of biological activity, we performed the semipreparative chromatographic enantioseparation of the most potent, selective, and chiral compounds. The separated enantiomers were then submitted to in vitro biological evaluation. The selectivity of the (-)-(S)-1 enantiomer against MAO-B increases twice and a half, while the selectivity of the (-)-(S)-4 enantiomer against MAO-A triples. Both the MAO-A and MAO-B isoforms respectively of the 1O5W and 1GOS models deposited in the Protein Data Bank were considered in the computational study. The docking study was carried out using several computational approaches with the aim of proposing possible binding modes of the MAO enantioselective compounds 1 and 4.

Objectives: The aim of this study was to investigate the in vitro antifungal activity of an isothiosemicarbazone cyclic analogue against isolates of Candida spp. including fluconazole-resistant Candida albicans., Methods: We investigated the activity of 2-cyclohexylidenhydrazo-4-phenyl-thiazole (EM-01D2) against 114 clinical isolates of Candida spp., representing five different species, by microdilution, according to the NCCLS method 27-A. The activity against C. albicans biofilms was also investigated. Toxicity in vitro was evaluated by MTT reduction assay., Results: EM-01D2 demonstrated low toxicity, broad spectrum, fungicidal activity and was active against C. albicans and Candida krusei at concentrations lower than those shown by amphotericin B and fluconazole (P < 0.05). It maintained potent in vitro activity against fluconazole-resistant C. albicans isolates. Fungicidal activity occurred at concentrations 1-2 doubling dilutions greater than the corresponding MICs, and time-kill analysis indicated that a 99.9% loss of C. albicans viability occurred after 6 h of incubation in the presence of EM-01D2 at concentrations equal to four times the MIC. EM-01D2 was also active in inhibiting the growth of C. albicans ATCC 10231 biofilms, even though such inhibition occurred at concentrations higher than the MICs determined under planktonic growth conditions. However, when C. albicans biofilms were pre-exposed to subinhibitory concentrations of EM-01D2, a reduction of MIC50 of amphotericin B was observed., Conclusions: Based on these results, EM-01D2 could represent a template for the development of novel fungicidal agents.

We demonstrate the possibility of using a femtosecond laser to measure with high accuracy the frequency of a far-infrared (FIR) monochromatic source, such as an optically pumped molecular laser, by generating in a suitable mixer a signal in the radio-frequency region at the frequency difference between n steps of a femtosecond comb and the FIR source. All the couples of modes lying a distance of n steps from one another contribute coherently to the heterodyne signal. The technique has been tested up to 670 GHz.

The synthesis of some aroylisothiosemicarbazides was accomplished and their biological activity against bacteria, fungi, and mycobacteria was investigated. Different synthetic pathways were followed according to the kind of substituents that were introduced on both the aroyl ring and the sulfur atom. Anti-bacterial activity was measured against Staphylococcus aureus, S. epidermidis, Streptococcus agalactiae and S. faecalis, Escherichia coli, and Salmonella typhi, while antifungal activity was evaluated against C. albicans. Two species, Mycobacterium tuberculosis H37RV and Mycobacterium avium ATCC19421, were employed to evaluate antimycobacterial activity.

We report on a case of reversible Pisa syndrome developed after treatment with galantamine in a patient with Alzheimer's disease without previous exposure to neuroleptic or other cholinesterase inhibitors. Complete and persistent resolution of the syndrome was achieved several weeks after botulinum toxin type-A injection., ((c) 2004 Movement Disorder Society.)

The effect of GuHCl and of NaCl on the structural properties of the hemocyanin (Hc) from Carcinus aestuarii has been studied by small angle x-ray scattering (SAXS) using synchrotron radiation. SAXS data collected as a function of perturbant concentration have been used to analyze conformational states of hexameric holo and apoHc as well as the holo and apoforms of the monomeric subunit CaeSS2. In the case of the holoprotein in GuHCl, two concentration domains were identified: at lower concentration, the perturbant induces aggregation of Hc molecules, whereas at higher concentration the aggregates dissociate with concomitant denaturation of the protein. In contrast, with apoHc the denaturation occurs at rather low GuHCl, pointing to an important effect of the active site bound copper for the stabilization of Hc tertiary structure. The effects of NaCl are similar to those of GuHCl as far as CaeSS2 is concerned, namely oligomerization precedes denaturation, whereas in the case of the hexameric form no aggregation occurs. To improve data analysis, on the basis of the current models for Hc monomers and oligomers, the fraction of each aggregation state and/or unfolded protein has been determined by fitting experimental SAXS curves with form factors calculated from Monte Carlo methods. In addition, a global analysis has been carried out on the basis of a thermodynamic model involving an equilibrium between a monomer in a nativelike and denatured form as well as a class of equilibria among the monomer and other aggregates.

Several arylideneisothiosemicarbazones and arylidenehydrazothiazoles have been synthesised to obtain new antimicrobial agents. Their activity against both bacteria and fungi has been tested and some interesting informations about their biological activity have been obtained.

It is known that some derivatives of both thiourea and thiosemicarbazide exhibit potent anti-microbial activity. In order to investigate the effects on the biological properties of structural modifications of such structures, we have synthesised and studied some arylidenisothiosemicarbazones. In this paper we report on the synthesis and structure-activity relationships of some isothiosemicarbazones, where the arylidene group has been replaced with a cycloalkyl group and the sulfur atom has been either differently substituted or enclosed in a thiazole ring.

9,10-Anthracenedione derivatives are known to exhibit a quite potent anticancer activity. It has also been reported that these compounds can be effectively employed in both antibacterial and antitrypanosomal therapy. Anthraquinones also exhibit some undesirable side effects, like cardiotoxicity. So many interactions seem to demonstrate that 9,10-anthracenediones strongly interact with a number of biological sites. In this paper we wish to report on the synthesis and the pharmaceutical activity of some newly synthesised derivatives containing the anthraquinone pharmacophore.

A set of aminoalkoxy-substituted, differently annullated furocoumarins, differing in the position of the aminoalkoxy chain and in the unsaturation level of the fused ring, has been subjected to electron impact and electrospray ionisation (ESI) experiments. In order to achieve a distinct characterisation of isomeric compounds, which partially failed under electron impact conditions, collision-induced dissociation experiments were performed on protonated molecules. The breakdown curves obtained by varying the tickle voltage on an ion trap ESI instrument led to the desired characterisation., (Copyright 2001 John Wiley & Sons, Ltd.)

Arylidenimidazoles bearing a thioethereal function in the position 2 of the imidazole ring show good antimicrobial activity. We now report on the synthesis and the biological properties of some novel arylidenisothiosemicarbazones, structurally related to the arylideneiminoimidazoles of which they can be considered the linear precursors. Particular attention has been put on the influence of structural modifications on the biological activity.

In this study some cycloalkyl-3-(N-substituted carbamoyl)-1-phenylpyrazoles have been synthesized in order to screen their capability to inhibit human cyclooxygenase. The synthetic pathway is based on the well known property of nitrilimines to undergo 1,3-dipolar cycloaddition reactions. The structures of all the synthesized compounds have been elucidated by means of both analytical and spectroscopic methods.

This work investigates the structure of native calf thymus chromatin as a function of fiber length and isolation procedures by using X-ray small angle scattering technique. Two methods of chromatin isolation have been compared in order to better understand the differences reported by various authors in terms of chromatin high order structure. In addition to these experimental results the effects of shearing have also been studied. In order to explain the differences among these chromatin preparations we built several models of chromatin fibers (represented as a chain of spherical subunits) assuming increasing level of condensation at increasing salt concentrations. For all these fiber models the corresponding theoretical X-ray scattering curves have been calculated and these results have been used to explain the influence of fiber length on the scattering profiles of chromatin. The comparison between experimental and theoretical curves confirms that the high molecular weight chromatin-DNA prepared by hypotonic swelling of nuclei (without enzymatic digestion) displays a partially folded structure even at low ionic strength, whereas the low molecular weight chromatin-DNA prepared by a brief nuclease digestion appears very weakly folded at the same ionic conditions.

The influence of epicuticular waxes extracted from different fruits on the photodegradation of pirimicarb (I) in the solid phase was studied. Waxes were extracted with CHCl(3) and CHCl(3)/CH(3)OH from nectarines (N), oranges (O(R)), and mandarin oranges (M). All of the waxes affect the qualitative behavior of the photodegradation of I: the formation of photoproducts N-formylpirimicarb (II) and demethylpirimicarb (III) was hindered. This influence was found to be independent of the light sources (sunlight or lamp > 290 nm) and of the solvents employed in the extraction of the waxes. The photodegradation rate (K(obs)) of I was reduced to a different extent by the presence of waxes, from N and O, and was increased from M (irrespective of the extraction solvent). The photodegradation rates of II and III were both reduced by all waxes, M included. The waxes extracted with CHCl(3)/CH(3)OH show a higher inhibition effect on K(obs) than those with CHCl(3). The scales of rate reduction were similar under sunlight and artificial light. Inhibition of the photodegradation rate does not correlate with UV absorbance of waxes or with their content on the surface of the fruits.

Ewe milk and ewe cheese samples were analysed by matrix-assisted laser desorption/ionization mass spectrometry and their protein profiles were compared with those obtained from bovine milk and bovine cheeses. Various mixtures of bovine and ewe cheeses in different weight ratios were analysed, leading to a reproducible calibration curve, which has been successfully employed in determining the percentage of bovine milk fraudulently added to ewe milk in the production of marketed ewe cheese.

This paper reports the synthesis and the study of a few new diastereomeric arylmethylcycloalkylamines, tested as potential dopamine receptor active agents. New procedures for the stereospecific synthesis of the arylmethylcycloalkylamines were successfully experimented. All the considered compounds did not show any appreciable dopamine receptor activity.

This paper reports the synthesis of a novel class of macrocyclic tetraesters containing 1,3-butandiol sub-units by reacting the stannolan derivative of the diol with diacyl chloride. The structure of the possible isomers was assigned by spectroscopic data and comparison with samples otherwise prepared. Preliminary screening revealed that these compounds have low antimicrobial activity, although it is higher than that of the starting diol.

Laser cooling in a Mg atomic beam is reported for the first time to our knowledge. Previous cooling experiments were performed by using visible or infrared lasers. The Mg atoms were cooled by using an intracavity frequency-doubled dye laser at 285 nm to reach the resonant (1)S(0)-(1)P(1) transition. Evidence of laser cooling was obtained even with the limited available laser power ( approximately 1-2 mW).