Synthesis and SAR-study for novel arylpiperazine derivatives of 5-arylidenehydantoin with α₁-adrenoceptor antagonistic properties

The study is focused on a series of 5-arylidenehydantoin derivatives with a phenylpiperazine-hydroxypropyl fragment at N3 of the hydantoin ring. The compounds were assessed on their affinity for α(1)-adrenoceptors and evaluated in functional bioassays for their antagonistic properties. Crystal structures of (Z)-5-(4-chlorobenzylidene)-3-(3-(4-(2-ethoxyphenyl)piperazin-1-yl)-2-hydroxypropyl)imidazolidine-2,4-dione (7) and hydrochloride of (Z)-5-(4-chlorobenzylidene)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)imidazolidine-2,4-dione (10a) were solved using the X-ray diffraction method. Classical molecular mechanics (MMFFs force field, MCMM, MacroModel) were used to predict 3D structure of compounds 5a-18a using a crystal structure of 7. SAR analysis was performed on the basis of Barbaro's pharmacophore model and structural properties of previously investigated α(1)-adrenoceptor antagonists possessing a hydantoin fragment. Most of the compounds exhibited significant affinities for α(1)-ARs in nanomolar range (40-290 nM). The highest activities (K(i)<75 nM) were observed for compounds possessing a 2-alkoxyphenylpiperazine fragment and two methoxy substituents at the benzylidene moiety. The results indicated that chemical properties, number and positions of substituents at the 5-arylidene fragment influenced the power of α(1)-affinities as follows: 3,4-di CH(3)O>2,4-di CH(3)O>4-Cl>2,3-di CH(3)O>H>4-N(CH(3))(2).     

Identification and characterization of transposable elements of Paracoccus pantotrophus

We studied diversity and distribution of transposable elements residing in different strains (DSM 11072, DSM 11073, DSM 65, and LMD 82.5) of a soil bacterium Paracoccus pantotrophus (alpha-Proteobacteria). With application of a shuttle entrapment vector pMEC1, several novel insertion sequences (ISs) and transposons (Tns) have been identified. They were sequenced and subjected to detailed comparative analysis, which allowed their characterization (i.e., identification of transposase genes, terminal inverted repeats, as well as target sequences) and classification into the appropriate IS or Tn families. The frequency of transposition of these elements varied and ranged from 10(-6) to 10(-3) depending on the strain. The copy number, localization (plasmid or chromosome), and distribution of these elements in the Paracoccus species P. pantotrophus, P. denitrificans, P. methylutens, P. solventivorans, and P. versutus were analyzed. This allowed us to distinguish elements that are common in paracocci (ISPpa2, ISPpa3--both of the IS5 family--and ISPpa5 of IS66 family) as well as strain-specific ones (ISPpa1 of the IS256 family, ISPpa4 of the IS5 family, and Tn3434 and Tn5393 of the Tn3 family), acquired by lateral transfer events. These elements will be of a great value in the design of new genetic tools for paracocci, since only one element (IS1248 of P. denitrificans) has been described so far in this genus.     

Construction and preliminary characterisation of mini-derivatives of a large (107-kb) cryptic plasmid of the sulfur bacterium Thiobacillus versutus

Abstract Several mini-replicons, derivatives of a large (107-kb) cryptic Thiobacillus versutus pTAV1 plasmid, were obtained. The pTAV1 derivatives confer all functions sufficient for autonomous replication in T. versutus but they cannot be maintained in Escherichia coli . The fragment of pTAV1 (4-kb) included in the smallest mini-replicon, pTAV202, encodes for two proteins of approximately 26 and 45 kDa. The region responsible for stable maintenance of pTAV1 derivatives (and presumably entire pTAV1) was located in defined 14-kb fragment of pTAV1 genome. Hybrid plasmids composed of E. coli vectors (pBGS18 or pWSK29) and pTAV202 replicon were constructed and their activity in both hosts tested.     

The effect of industrial pollution on copper,lead, zinc and cadmium concentration in xylem rings of resistant (Populus marilandica) and sensitive (P. balsamifera) species of poplar

Summary The patterns of radial distribution of copper, lead, zinc and cadmium in two species of poplar, growing under polluted conditions near a copper smelter, were investigated. Populus marilandica is very resistant to such pollution, but P. balsamifera is sensitive. Soils were examined for concentrations of these metals, and only a surface layer of soil was polluted with copper and lead. P. balsamifera absorbed much more cadmium than P. marilandica under the same conditions. P. marilandica shows a pattern of copper radial distribution with significantly increased concentration of the meral in the layers in the middle of the trunk compared to P. balsamifera. Zinc and cadmium have a pattern with increased metal concentration from the bark towards the pith of the tree. In the case of copper and lead the pattern indicates increased concentrations of these metals in the rings adjacent to the pith while the pattern in other parts of the tree remains unconfirmed due to poor precision. Poplar xylem seems to accumulate zinc and cadmium while the content of lead in xylem is much lower than in the adjacent soil.This paper is dedicated to the memory of Professor Stefan Bialobok, Institute of Dendrology, Polish Academy of Sciences in Kornik     

Modes of morphogenesis inheritance in vitro in strawberry (<Emphasis Type="Italic">Fragaria x ananassa</Emphasis> Duch.)

The phenomenon of morphogenesis observed in in vitro cultures, as the ability of cultured cells and/or plant tissues to regenerate into a complete plant, is used for propagation of orchard species plants of the genus Fragaria spp. Genetic mechanisms controlling the in vitro morphogenesis process are still not fully understood. Research has been conducted to broaden knowledge about the genetic control of this process. The aim of this study was to determine the effect of cytoplasmic loci on the inheritance of the cell morphogenetic potential within the species Fragaria x ananassa. The study included five strawberry cultivars—‘Dukat’, ‘Jota’, ‘Temptation’, ‘Pastel’ and ‘Senga Sengana’. The third Griffing method of diallel crossing was fully useful for achieving the purpose of the research, because it allowed, by comparing the effects of reciprocal crosses for each crossing combination, determining the possible impact of cytoplasmic loci on the inheritance of morphogenetic abilities in the analyzed cultivars. Evaluation of the effects of reciprocal crosses showed different modes of inheritance of the morphogenetic potential in vitro of plant cells of these strawberry cultivars. The strawberry cultivar ‘Dukat’ transmitted genetic determinants of the morphogenetic potential cytoplasmically. Nuclear transmission of the morphogenetic potential was recorded for the cultivar ‘Senga Sengana’. ‘Jota’, ‘Temptation’ and ‘Pastel’ cultivars passed on this trait in a cytoplasmic-nuclear mode. Morphogenesis efficiency of hybrids, whose maternal forms transmitted the morphogenetic potential in a cytoplasmic-nuclear mode, depended likely on the interaction between the maternal plasmotype and the paternal nuclear genes.     

The effect of immobilization on body fluid volume in the rat

Total body water (TBW) and extracellular volume (EVC) were measured simultaneously with³H and⁸²Br in male albino rats after two, four and eight weeks of immobilization. On the basis of these measurements the intracellular fluid volume (ICV) was calculated. It was found that immobilization caused no changes in the volume and distribution of body fluids.     

Stereochemistry of Internucleotide Bond Formation by the H-Phosphonate Method. 1. Synthesis and 31P Nmr Analysis of 16 Diribonulceoside (3′-5′)-H-Phosphonates and the Corresponding Phosphorothioates

Sixteen diribonucleoside (3′-5′)-H-phosphonates were synthesized via condensation of the protected ribonucleoside 3′-H-phosphonates with nucleosides, and the influence of a nucleoside sequence on the observed stereoselectivity was analyzed. ₃₁P NMR spectroscopy was used to evaluate a relationship between chemical shift and absolute configuration at the phosphorous center of the H-phosphonate diesters as well as of the corresponding phosphorothioate diesters. Although for the most cases such correlation was found, there was however several exceptions to the rule where the relative positions of resonances arising from R _P and S _P diastereomers were reversed.