Synthesis of a new class of uridine phosphorylase inhibitors

A new series of potent uridine phosphorylase inhibitors have been prepared from barbituric acid. Among them, 1-[(2-hydroxyethoxy)methyl]-5-)(m--benzyloxy)benzylbarbituric acid ( 37 , BBBA) is the most promising having a K_i value of 1.1 ± 0.2 nM with uridine phosphorylase from human liver. The new inhibitors are easily synthesized and are better inhibitors of human uridine phosphorylase than their uracil counterparts.     

Synthesis,and Antimycobacterial and Cytotoxic Evaluation of Certain Fluoroquinolone Derivatives

Certain 1‐ethyl‐ and 1‐aryl‐6‐fluoro‐1,4‐dihydroquinol‐4‐one derivatives were synthesized and evaluated for antimycobacterial and cytotoxic activities. Preliminary results indicated that, for 1‐aryl‐6‐fluoroquinolones, both 7‐(piperazin‐1‐yl)‐ and 7‐(4‐methylpiperazin‐1‐yl) derivatives, 9b and 11a , are able to completely inhibit the growth of M. tuberculosis at a concentration of 6.25 μg/ml, while the 7‐[4‐(2‐oxo‐2‐phenylethyl)piperazin‐1‐yl] derivative 13 exhibits only 31% growth inhibition at the same concentration. For 1‐ethyl‐6‐fluoroquinolones, both 7‐[4‐(2‐oxopropyl)piperazin‐1‐yl]‐ and 7‐[4‐(2‐oxo‐2‐phenylethyl)piperazin‐1‐yl]‐derivatives, 2a and 2b , respectively, show complete inhibition, while their 2‐iminoethyl and substituted phenyl counterparts 3a and 2c are less active. In addition, the 6,8‐difluoro derivative was a more‐favorable inhibitor than its 6‐fluoro counterpart ( 2b vs. 2d ). These results deserve full attention especially because 2a, 2b, 9b , and 11a are non‐cytotoxic at a concentration of 100 μM . Furthermore, compound 9b proved to be a potent anti‐TB agent with selective index (SI)>40 and an EC₉₀ value of 5.75 μg/ml.     

Simultaneous determination of thymidylate and thymidine diphosphate by capillary electrophoresis as a rapid monitoring tool for thymidine kinase and thymidylate kinase activities

A simple and rapid capillary electrophoretic method was developed for the simultaneous determination of thymidylate (TMP) and thymidine 5'-diphosphate (TDP) in enzyme assays without using radioactive-labeled substrates. Prior to electrophoretic separation, addition of acetonitrile and sodium chloride to the assay solution and brief centrifugation are recommended for the purpose of sample cleanup and sample stacking. The separation of micromolar TMP and TDP from millimolar adenosine 5'-triphosphate (ATP) was performed at 25 degrees C using sodium tetraborate as the background electrolyte. Under the optimal condition, a good separation with high efficiency was achieved in 6 min. Several parameters affecting the separation were studied, including the pH of electrolyte, the applied voltage, and acetonitrile-salt sample stacking. The fronting of the ATP peak resulting from the interference of magnesium ion in the enzyme assay buffer was suppressed by the addition of sodium ethylenediaminetetraacetate to the sample solution. Using deoxyadenylate as an internal standard, the linear range of the method was 5-200 microM, and the concentration limits of detection of TMP and TDP were 2.6 and 3.8 microM, respectively. Application of the proposed method for simultaneous determination of TMP and TDP in enzyme assays was demonstrated by the activity assays of thymidine kinase and thymidylate kinase from white spot syndrome virus. This is a sensitive, nonradioactive method for thymidine kinase and thymidylate kinase assays.     

Palladacyclic complexes bearing CNN-type ligands as catalysts in the Heck reaction

Preparations of novel unsymmetrical, tridentate nitrogen ligand precursors, PhN=C(CMe2)(NPh)C=N(CH2)2NMe2(1) and PhN=C(CMe2)(NPh)C=N(CH2)Py (2), are described. Treatment of 1 with 1 molar equiv. (COD)PdCl2 in the presence of NEt3 or with 1 molar equiv. Pd(OAc)2 affords orthometallated palladium(II) complexes, [PhN=C(CMe2)(N-eta1-Ph)C=N(CH2)2NMe2]PdX (X=Cl (3); X=OAc (4)), respectively. Compound can be yielded via the reaction of with an excess of LiCl in methanol. Treatment of with 1 molar equiv. of (COD)PdCl2, Pd(OAc)2 or Pd(TFA)2 affords orthometallated palladium(II) complexes, [PhN=C(CMe2)(N-eta1-Ph)C=NCH2Py]PdX (X=Cl (5); X=OAc (6); X=TFA (7)), respectively. The crystal and molecular structures are reported for compounds 2, 3, 5 and 6. The application of these novel palladacyclic complexes to the Heck reaction with aryl halide substrates was examined.     

Novel determination of the dimerization mechanism for thermal polymerization of α-methylstyrene

This study discussed the phenomena on thermal polymerization of α-methylstyrene (AMS). A curve scanned by temperature-programmed technique was performed by differential scanning calorimetry (DSC). Heat of polymerization (ΔH) and onset temperature of exothermic (T₀) behavior were determined to be 280±10 J g^-1 and about 138±1°C, respectively. A dimer formation mechanism was proposed for initiation of the propagating chain. Spectroscopic identification of dimer structure was conducted by infrared (IR) spectroscopy in the wavenumber from 650 to 1100 cm^-1associated with molecular fingerprint characteristics. The mechanism of thermal polymerization on α-methylstyrene proposed in this study was similar to that of styrene suggested by Mayo.     

Mass analyzed threshold ionization spectroscopy of 7-azaindole cation

The vibrationally resolved mass analyzed threshold ionization (MATI) spectra of jet-cooled 7-azaindole have been recorded by ionizing via four different intermediate levels. The adiabatic ionization energy of this molecule is determined to be 65 462±5 cm⁻¹, which is greater than that of indole by 2871 cm⁻¹. The vibrational spectra of 7-azaindole in the S₁ and D₀ states have been successfully assigned by comparing the measured frequencies with those of indole as well as the predicted values from the ab initio calculations. Detailed analysis on the MATI spectra shows that the structure of the cation is somewhat different from that of this species in the neutral S₁ state.     

Synthesis and Cytotoxicity Evaluation of Metal‐Chelator‐Bearing Flavone,Carbazole, Dibenzofuran,Xanthone, and Anthraquinone

2‐(Aryloxymethyl)‐5‐benzyloxy‐1‐methyl‐1H‐pyridin‐4‐ones 8a – 8g , 2‐(aryloxymethyl)‐5‐hydroxy‐4H‐pyran‐4‐ones 9a – 9g , and 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a – 10g were prepared from the known 5‐benzyloxy‐2‐(hydroxymethyl)pyran‐4‐one ( 3 ) in a good overall yield. These compounds were evaluated in vitro against a three‐cell lines panel consisting of MCF7 (breast), NCI‐H460 (lung), and SF‐268 (CNS), and the active compounds passed on for evaluation in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results indicated that 5‐hydroxy derivatives are more favorable than their corresponding 5‐benzyloxy precursors ( 10a – 10g vs. 8a – 8g ), and 1‐methyl‐1H‐pyridin‐4‐ones are more favorable than their corresponding pyran‐4(1H)‐ones ( 10a – 10g vs. 9a – 9g ). Among these three types of compounds, 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a – 10g were the most cytotoxic; they inhibited the growth of almost all the cancer cells tested. On the contrary, compound 8a (a mean GI₅₀=27.8 μM ), 8b (38.5), 8d (11.0), and 8e (30.5) are especially active against the growth of SK‐MEL‐5 (a melanoma cancer cell) with a GI₅₀ of <0.01, 5.65, 0.55, and 0.03 μM , respectively (cf. Table 2).     

Dense stars with exotic configurations

In this paper, we consider dense stars with configurations expected from the SU(3)_C×SU(2)_W× U(1) standard model of strong and electroweak interactions. Following a recent suggestion that strange matter, a form of (uds) quark matter, may be the true ground state of hadronic matter, we investigate the prospect for the existence of dense stars consisting partially, or entirely, of strange matter by comparing the relative stability between neutron matter and strange matter. It is found that the restriction on the maximum star mass holds in all cases, including a pure strange star, a pure neutron star, and a neutron star with a quark core. It is also found that the choice of both the bag constantB and the strong coupling constant _s has a decisive effect on the relative stability between strange matter and neutron matter. For currently accepted values of (B, _s), anA= dense starcannot consist entirely,nor partially, of strange matter. Nevertheless, such conclusion may be subject to change if corrections ofO ( _s ² ) or other effects are taken into account. Finally, we use the framework of Tolman, Oppenheimer, and Volkoff to analyze two cases of boson stars: gluon stars and stars consisting of massive scalar particles (massive bosons). It is found that, in the case of gluon stars, the presence of the bag constant in the QCD vacuum yields results very similar to that found in quark stars. On the other hand, soliton stars consisting of massive bosons exist if there is some background pressure which plays the role similar to the bag constant for lowering the matter pressure. The stability problem for both gluon stars and soliton stars is briefly discussed.