Impact of copper and iron binding properties on the anticancer activity of 8-hydroxyquinoline derived Mannich bases.

The anticancer activity of 8-hydroxyquinolines relies on complex formation with redox active copper and iron ions. Here we employ UV-visible spectrophotometry and EPR spectroscopy to compare proton dissociation and complex formation processes of the reference compound 8-hydroxyquinoline (Q-1) and three related Mannich bases to reveal possible correlations with biological activity. The studied derivatives harbor a CH2-N moiety at position 7 linked to morpholine (Q-2), piperidine (Q-3), and chlorine and fluorobenzylamino (Q-4) substituents. Solid phase structures of Q-3, Q-4·HCl·H2O, [(Cu(HQ-2)2)2]·(CH3OH)2·Cl4·(H2O)2, [Cu(Q-3)2]·Cl2 and [Cu(HQ-4)2(CH3OH)]·ZnCl4·CH3OH were characterized by single-crystal X-ray diffraction analysis. In addition, the redox properties of the copper and iron complexes were studied by cyclic voltammetry, and the direct reaction with physiologically relevant reductants (glutathione and ascorbic acid) was monitored. In vitro cytotoxicity studies conducted with the human uterine sarcoma MES-SA/Dx5 cell line reveal the significant cytotoxicity of Q-2, Q-3, and Q-4 in the sub- to low micromolar range (IC50 values 0.2-3.3 μM). Correlation analysis of the anticancer activity and the metal binding properties of the compound series indicates that, at physiological pH, weaker copper(ii) and iron(iii) binding results in elevated toxicity (e.g.Q4: pCu = 13.0, pFe = 6.8, IC50 = 0.2 μM vs.Q1: pCu = 15.1, pFe = 13.0 IC50 = 2.5 μM). Although the studied 8-hydroxyquinolines preferentially bind copper(ii) over iron(iii), the cyclic voltammetry data revealed that the more cytotoxic ligands preferentially stabilize the lower oxidation state of the metal ions. A linear relationship between the pKa (OH) and IC50 values of the studied 8-hydroxyquinolines was found. In summary, we identify Q-4 as a potent and selective anticancer candidate with significant toxicity in drug resistant cells

Eruptive history of the Late Quaternary Ciomadul (Csomád) volcano, East Carpathians, part II: magma output rates

This study, which builds on high-precision unspiked Cassignol-Gillot K-Ar age determinations, presents an advanced DEMbased volumetrical analysis to infer long-term magma output rates for the Late Quaternary Ciomadul (Csomád) dacitic lava dome complex (East Carpathians, Romania). The volcanic field of Ciomadul developed on the erosional surface of Lower Cretaceous flysch and ~ 2 Ma old andesites and experienced an extended eruptive history from ~ 850 to < 30 ka. Predominantly effusive activity took place during the first stage (~ 850 to ~ 440 ka), producing volumetrically minor, isolated, peripheral domes. Subsequently, after a ~ 250 ky repose interval, a voluminous central dome cluster developed in the second stage (~ 200 to < 30 ka). During the youngest phase of evolution (~ 60 to < 30 ka), highly explosive eruptions also occurred, resulting in the formation of two craters (Mohos and St. Ana). The calculated ~ 8.00 ± 0.55 km3 total volume of the lava domes, which includes the related volcaniclastic (1.57 km3 ) as well as erosionally removed (0.18 km3 ) material, is in line with dimensions of other medium-sized dacitic lava domes worldwide. This volume was extruded at an average long-term magma output rate of 9.76 km3 / My (0.0098 km3 /ky). However, most of the domes (7.53 ± 0.51 km3 ) were formed in the 200 to < 30 ka period, implying a significantly increased magma output rate of 37.40 km3 /My (0.0374 km3 /ky), more than 30 times higher than in the first stage. Within these long-term trends, individual lava domes of Ciomadul (e.g. those with volumes between 0.02 and 0.40 km3 ) would have been emplaced at much higher rates over a period of years to tens of years. The active periods, lasting up to hundreds of years, would have been followed by repose periods ~ 30 times longer. The most recent eruption of Ciomadul has been dated here at 27.7 ± 1.4 ka. This age, which is in agreement with radiocarbon dates for the onset of lake sediment accumulation in St. Ana crater, dates fragmented lava blocks which are possibly related to a disrupted dome. This suggests that during the last, typically explosive, phase of Ciomadul, lava dome extrusion was still ongoing. In a global context, the analysis of the volumetric dynamism of Ciomadul’s activity gives insights into the temporal variations in magma output; at lava domes, short-term (dayor week-scale) eruption rates smooth out in long-term (millenia-scale) output rates which are tens of times lower

Wheat-barley hybridization – the last forty years

Abstract Several useful alien gene transfers have been reported from related species into wheat (Triticum aestivum), but very few publications have dealt with the development of wheat/barley (Hordeum vulgare) introgression lines. An overview is given here of wheat 9 barley hybridization over the last forty years, including the development of wheat 9 barley hybrids, and of addition and translocation lines with various barley cultivars. A short summary is also given of the wheat 9 barley hybrids produced with other Hordeum species. The meiotic pairing behaviour of wheat 9 barley hybrids is presented, with special regard to the detection of wheat– barley homoeologous pairing using the molecular cytogenetic technique GISH. The effect of in vitro multiplication on the genome composition of intergeneric hybrids is discussed, and the production and characterization of the latest wheat/barley translocation lines are presented. An overview of the agronomical traits (b-glucan content, earliness, salt tolerance, sprouting resistance, etc.) of the newly developed introgression lines is given. The exploitation and possible use of wheat/barley introgression lines for the most up-to-date molecular genetic studies (transcriptome analysis, sequencing of flow-sorted chromosomes) are also discussed

Ultrasound assisted casting of an AM60 based metal matrix nanocomposite, its properties, and recyclability

An AM60 magnesium alloy nanocomposite reinforced with 1 wt % of AlN nanoparticles was prepared using an ultrasound (US) assisted permanent-mould indirect-chill casting process. Ultrasonically generated cavitation and acoustic streaming promoted de-agglomeration of particle clusters and distributed the particles throughout the melt. Significant grain refinement due to nucleation on the AlN nanoparticles was accompanied by an exceptional improvement in properties: yield strength increased by 103%, ultimate tensile strength by 115%, and ductility by 140%. Although good grain refinement was observed, the large nucleation undercooling of 14 K limits further refinement because nucleation is prevented by the formation of a nucleation-free zone around each grain. To assess the industrial applicability and recyclability of the nanocomposite material in various casting processes, tests were performed to determine the effect of remelting on the microstructure. With each remelting, a small percentage of effective AlN nanoparticles was lost, and some grain growth was observed. However, even after the third remelting, excellent strength and ductility was retained. According to strengthening models, enhanced yield strength is mainly attributed to Hall-Petch strengthening caused by the refined grain size. A small additional contribution to strengthening is attributed to Orowan strengthening

Cytomolecular identification of individual wheat-wheat chromosome arm associations in wheat-rye hybrids

Chromosome pairing in the meiotic metaphase I of wheatrye hybrids has been characterized by sequential genomic and fluorescent in situ hybridization allowing not only the discrimination of wheat and rye chromosomes, but also the identification of the individual wheat and rye chromosome arms involved in the chromosome associations. The majority of associations (93.8%) were observed between the wheat chromosomes. The largest number of wheat-wheat chromosome associations (53%) was detected between the A and D genomes, while the frequency of B-D and A-B associations was significantly lower (32 and 8%, respectively). Among the A-D chromosome associations, pairing between the 3AL and 3DL arms was observed with the highest frequency, while the most frequent of all the chromosome associations (0.113/ cell) was found to be the 3DS-3BS. Differences in the pairing frequency of the individual chromosome arms of wheat-rye hybrids have been discussed in relation to the homoeologous relationships between the constituent genomes of hexaploid wheat