Synthesis,Characterization and In Vitro Evaluation of Novel 5-Ene-thiazolo[3,2-b][1,2,4]triazole-6(5H)-ones as Possible Anticancer Agents

The present paper is devoted to the search for drug-like molecules with anticancer properties using the thiazolo[3,2-b][1,2,4]triazole-6-one scaffold. A series of 24 novel thiazolo-[3,2-b][1,2,4]triazole-6-ones with 5-aryl(heteryl)idene- and 5-aminomethylidene-moieties has been synthesized employing three-component and three-stage synthetic protocols. A mixture of Z/E-isomers was obtained in solution for the synthesized 5-aminomethylidene-thiazolo[3,2-b]-[1,2,4]triazole-6-ones. The compounds have been studied for their antitumor activity in the NCI 60 lines screen. Some compounds present excellent anticancer properties at 10 μM. Derivatives 2h and 2i were the most active against cancer cell lines without causing toxicity to normal somatic (HEK293) cells. A preliminary SAR study had been performed for the synthesized compounds.     

69mZn-containing radiopharmaceuticals: a novel approach to molecular design

^69mZn was produced and separated for medical applications. Possibilities and perspectives for production of radiopharmaceuticals based on ^69mZn containing derivatives of thiazine, thiazoline and thiourea are considered. Each one of the latters is a zinc chelator and a nitric oxide synthase (NOS) effector at the same time. Cytotoxic effect of NOS activator and NOS inhibitors are shown in experiments with HL-60, K-562 and MOLT-4 cell lines and in bone marrow cells of the acute B-lymphoblastic leukemia patients. Some of those compounds are worthy to get selected for further application as radiopharmaceuticals including their antitumor speciements.

     

Magnetic-field-induced spin excitations and renormalized spin gap of the underdoped La1.895Sr0.105CuO4 superconductor

High-resolution neutron inelastic scattering experiments in applied magnetic fields have been performed on La1.895Sr0.105CuO4 (LSCO). In zero field, the temperature dependence of the low-energy peak intensity at the incommensurate momentum transfer QIC=(0.5,0.5+/-delta,0),(0.5+/-delta,0.5,0) exhibits an anomaly at the superconducting Tc which broadens and shifts to lower temperature upon the application of a magnetic field along the c axis. A field-induced enhancement of the spectral weight is observed, but only at finite energy transfers and in an intermediate temperature range. These observations establish the opening of a strongly downward renormalized spin gap in the underdoped regime of LSCO. This behavior contrasts with the observed doping dependence of most electronic energy features.     

Analysis of cardiovascular oscillations: a new approach to the early prediction of pre-eclampsia

Pre-eclampsia (PE) is a serious disorder with high morbidity and mortality occurring during pregnancy; 3%-5% of all pregnant women are affected. Early prediction is still insufficient in clinical practice. Although most pre-eclamptic patients show pathological uterine perfusion in the second trimester, this parameter has a positive predictive accuracy of only 30%, which makes it unsuitable for early, reliable prediction. The study is based on the hypothesis that alterations in cardiovascular regulatory behavior can be used to predict PE. Ninety-six pregnant women in whom Doppler investigation detected perfusion disorders of the uterine arteries were included in the study. Twenty-four of these pregnant women developed PE after the 30th week of gestation. During pregnancy, additional several noninvasive continuous blood pressure recordings were made over 30 min under resting conditions by means of a finger cuff. The time series extracted of systolic as well as diastolic beat-to-beat pressures and the heart rate were studied by variability and coupling analysis to find predictive factors preceding genesis of the disease. In the period between the 18th and 26th weeks of pregnancy, three special variability and baroreflex parameters were able to predict PE several weeks before clinical manifestation. Discriminant function analysis of these parameters was able to predict PE with a sensitivity and specificity of 87.5% and a positive predictive value of 70%. The combined clinical assessment of uterine perfusion and cardiovascular variability demonstrates the best current prediction several weeks before clinical manifestation of PE.     

Synthesis,in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents

New potential bioactive oxazolopyrimidines have been synthesized using two main approaches: the pyrimidine ring annulation on a functionalized oxazole and the benzoyl bromide trimerization followed by rearrangement and formation of the oxazolo[5,4-d]pyrimidine scaffold. The docking analyzes have shown that 7-piperazine substituted oxazolo[4,5-d]pyrimidines 8a – 8c could be potential VEGFR2 inhibitors with high free energy of ligand–protein complex formation (ΔG: −10.1, −9.6, −9.8 kcal/mol, respectively). In vitro antitumor assays confirmed theoretical predictions that oxazolo[4,5-d]pyrimidines 8a – 8c containing positively charged piperazine moiety should demonstrate significantly higher cytotoxic effects. 4-[5-(4-Chlorophenyl)-2-phenyl[1,3]oxazolo[4,5-d]pyrimidin-7-yl]piperazin-1-ium trifluoroacetate ( 8c ) exhibited a slightly higher antiproliferative effect (IC₅₀=0.21 μm ) than doxorubicin (IC₅₀=0.36 μm ) on MDA-MB-231 cell line and has relatively good results on OVCAR-3 (IC₅₀=1.7 μm ) and HCT-116 (IC₅₀=0.24 μm ) cells.     

Structure–property relations for balsa wood as a function of density: modelling approach

In order to find an alternative core material to balsa wood in composite sandwich structures, it is important to understand balsa’s elastic properties in relation to its complex microstructural organisation. In the present work, experimental data on the elastic constants and microstructural features of balsa wood were collected for different porosities (densities) and processed into structure–property relations. An inverse problem was solved to predict variation of the cell wall properties with density, such that the collected experimental structure–property relations were satisfied. The Young’s modulus of the cell wall material in the longitudinal direction was found to increase with balsa’s density, which is consistent with the knowledge that the cell wall material stiffens during tree maturation. The value reported in the literature falls in the middle of the predicted range. The proposed micromechanical model also accurately calculated elastic properties of balsa wood at the mesolevel including longitudinal, radial, and tangential directions. The model took into account the presence of ray cells. It was shown that the addition of 15 % of rays increased the radial Young’s modulus up to 4 times with only slight decrease in the longitudinal modulus.     

The effect of ultrasonic and HNO3 treatment of activated carbon from fruit stones on capacitive and pseudocapacitive energy storage in electrochemical supercapacitors

The effect of ultrasonic treatment and modification with nitric acid of activated carbon obtained from fruit stones, on the parameters of electric double-layer (EDL) as well as on farad–volt characteristics of its boundary with electrolyte 7.6 m KОН, 4 m KI and 2 m ZnI₂ aqueous solutions has been studied by means of precision porometry, cyclic voltamperometry, electrochemical impedance spectroscopy and computer simulation methods. It is shown that HNO₃ treatment results in an increase of the electrostatic capacitance up to 202 F/g in 7.6 m KОН-solution as well as pseudocapacitance up to 1250 F/g in 4 m KI. This increase is supposed to be related both with hydrophilicity and with an increase of the density of states on Fermi level. The ultrasonic treatment enables one to significantly increase (more than 200 times) the density of states on Fermi level which in turn causes both quantitative and qualitative changes in farad–volt dependences. A hybrid supercapacitor with specific capacitance of 1100 F/g and specific energy of 49 Wh/kg per active mass of two electrodes was developed.