Synthesis,Molecular Modeling,and Biological Evaluation of Novel Chiral Thiosemicarbazone Derivatives as Potent Anticancer Agents

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF‐7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC‐27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound 17b exhibited the most potent activity (IC₅₀ 4.6 μM) against HGC‐27 as compared with the reference compound, sindaxel (IC₅₀ 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. Chirality 27:177–188, 2015. © 2014 Wiley Periodicals, Inc.     

Aluminum Toxicity: A Case Study on Tobacco (<i>Nicotiana tabacum</i> L.)

Aluminum is an abundant metal in the earth’s crust that turns out to be toxic in acidic environments. Many plants are affected by the presence of aluminum at the whole plant level, at the organ level, and at the cellular level. Tobacco as a cash crop (Nicotiana tabacum L.) is a widely cultivated plant worldwide and is also a good model organism for research. Although there are many articles on Al-phytotoxicity in the literature, reviews on a single species that are economically and scientifically important are limited. In this article, we not only provide the biology associated with tobacco Al-toxicity, but also some essential information regarding the effects of this metal on other plant species (even animals). This review provides information on aluminum localization and uptake process by different staining techniques, as well as the effects of its toxicity at different compartment levels and the physiological consequences derived from them. In addition, molecular studies in recent years have reported specific responses to Al toxicity, such as overexpression of various protective proteins. Besides, this review discusses data on various organelle-based responses, cell death, and other mechanisms, data on tobacco plants and other kingdoms relevant to these studies.     

Effect of Axial Ligand Length on Biological and Anticancer Properties of Axially Disubstituted Silicon Phthalocyanines

In this study, three new axially disubstituted silicon phthalocyanines ( SiPc1–3 ) and their quaternized phthalocyanine derivatives ( QSiPc1–3 ) were prepared and characterized. The biological properties (antioxidant, antimicrobial, antibiofilm, and microbial cell viability activities) of the water-soluble silicon phthalocyanines were examined, as well. A 1 % DMSO diluted with pure water was used as a solvent in biological activity studies. All the compounds exhibited high antioxidant activity. They displayed efficient antimicrobial and antimicrobial photodynamic therapeutic properties against various microorganisms, especially Gram (+) bacteria. Additionally, they demonstrated high antibiofilm activities against S. aureus and P. aeruginosa. In addition, 100 % bacterial reduction was obtained for all the studied phthalocyanines against E. coli viable cells. Besides, the DNA cleavage and binding features of compounds ( QSiPc1–3 ) were studied using pBR322 DNA and CT-DNA, respectively. Furthermore, the human topoisomerase I enzyme inhibition activities of compounds QSiPc1 – 3 were studied. Anticancer properties of the water-soluble compounds were investigated using cell proliferation MTT assay. They exhibited anticarcinogenic activity against the human colon cancer cell line (DLD-1). Compounds QSiPc1 and QSiPc3 displayed a high anticarcinogenic effect on the DLD-1 cell line. The obtained results indicated that all the studied compounds may be effective biological agents and anticancer drugs after further investigations.     

Utilization of Response Surface Methodology in Optimization of Proline Extraction from Castanea sativa Honey

Proline constitutes approximately 85 % of the amino acid composition of honey. Therefore, the quantitative determination of this amino acid in honey samples is used by many national/international authorities to evaluate the quality of honey types. In this study, it was aimed to achieve maximum proline amino acid extraction from honey samples whose botanical origins were confirmed by melissopalynological analysis. For this reason, based on three different spectrophotometric methods used in the literature for proline analysis, proline extraction was optimized with the Response Surface Method (RSM) and Box-Behnken experimental design. Three independent variables were determined as treatment time (2, 6, and 10 min), treatment temperature (22, 46, and 70 °C), and cooling time (5, 25, and 45 min). As a result of the optimization, it was seen that only significantly effective independent variable on the proline content of honey was the processing temperature. The optimum conditions obtained as a result of the RSM were found to be 2 min for the treatment time, 70 °C for the treatment temperature and 45 min for the cooling time. The composite desirability of the optimum conditions (R²) was found to be 1.00. It was determined that the method proposed by International Honey Commission (IHC) is efficient for proline analysis, but it provides more proline extraction by reducing of time from 10 min to 2 min in hold time in boiling water bath only during the extraction step. As a result, the conditions to be used in order to achieve maximum proline extraction with different spectrophotometric methods were determined and optimum values were determined. In addition, since the botanical origin of honey samples significantly affects the proline content of honey, it can be suggested that this study be optimized for different monofloral honey samples as well.     

On the production,elemental composition (C,N, P) and distribution of photosynthetic organic matter in the Southern Black Sea

Chemical oceanographic understanding of the southernBlack Sea has been improved by recent measurements ofthe optical transparency, phytoplankton biomass (interms of chlorophyll-a and particulate organic matter)and primary productivity. During the spring-autmunperiod of 1995–1996, light generally penetrated onlyinto the upper 15–40 m, with an attenuation coefficientvarying between 0.125 and 0.350 m^2122;1. The averagechlorophyll-a (Chl-a) concentrations for the euphoticzone ranged from 0.1 to 1.5 μg l^2122;1. Coherentsub-surface Chl-a maxima were formed near the base ofthe euphotic zone only in summer. Production rate variedbetween 247 and 1925 in the spring and between 405 and687 mgC m^2122;2 d^2122;1 in the summer-autumn period.The average POM concentrations in the euphotic zonevaried regionally and seasonally between 3.8 and28.6 μm for POC, 0.5 and 3.1 μm for PON and0.02 and 0.1 μm for PP. Atomic ratios of C/N, C/Pand N/P, derived from the regressions of POM data,ranged between 7.5 and 9.6, 109 and 165, and 11.2 and16.6, respectively. In the suboxic/anoxic interface,the elemental ratios change substantially due to anaccumulation of PP cohering to Fe and Mn oxides. Thechemocline boundaries and the distinct chemicalfeatures of the oxic/anoxic transition layer (the so-called suboxic zone) are all located at specificdensity surfaces; however, they exhibit remarkablespatial and temporal variations both in their positionand in their magnitude, which permit the definition of long-term changes in the biochemical properties of theBlack Sea upper layer. This revised version was published online in July 2006 with corrections to the Cover Date.     

Molecular Co-occupancy Identifies Transcription Factor Binding Cooperativity In Vivo

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A Turkish family with Nance-Horan syndrome due to a novel mutation

Nance-Horan Syndrome (NHS) is a rare X-linked syndrome characterized by congenital cataract which leads to profound vision loss, characteristic dysmorphic features and specific dental anomalies. Microcornea, microphthalmia and mild or moderate mental retardation may accompany these features. Heterozygous females often manifest similarly but with less severe features than affected males. We describe two brothers who have the NHS phenotype and their carrier mother who had microcornea but not cataract. We identified a previously unreported frameshift mutation (c.558insA) in exon 1 of the NHS gene in these patients and their mother which is predicted to result in the incorporation of 11 aberrant amino acids prior to a stop codon (p.E186Efs11X). We also discussed genotype–phenotype correlation according to relevant literature.     

The tetrameric pheromone module SteC‐MkkB‐MpkB‐SteD regulates asexual sporulation,sclerotia formation and aflatoxin production in Aspergillus flavus

For eukaryotes like fungi to regulate biological responses to environmental stimuli, various signalling cascades are utilized, like the highly conserved mitogen‐activated protein kinase (MAPK) pathways. In the model fungus Aspergillus nidulans, a MAPK pathway known as the pheromone module regulates development and the production of secondary metabolites (SMs). This pathway consists five proteins, the three kinases SteC, MkkB and MpkB, the adaptor SteD and the scaffold HamE. In this study, homologs of these five pheromone module proteins have been identified in the plant and human pathogenic fungus Aspergillus flavus. We have shown that a tetrameric complex consisting of the three kinases and the SteD adaptor is assembled in this species. It was observed that this complex assembles in the cytoplasm and that MpkB translocates into the nucleus. Deletion of steC, mkkB, mpkB or steD results in abolishment of both asexual sporulation and sclerotia production. This complex is required for the positive regulation of aflatoxin production and negative regulation of various SMs, including leporin B and cyclopiazonic acid (CPA), likely via MpkB interactions in the nucleus. These data highlight the conservation of the pheromone module in Aspergillus species, signifying the importance of this pathway in regulating fungal development and secondary metabolism.     

The investigation of therapeutic potential of oxytocin and liraglutide on vincristine‐induced neuropathy in rats

The aim of this study was to assess the therapeutic potential of oxytocin and liraglutide (LIR), a GLP‐1 analogue, in a rat model of vincristine‐induced neuropathy. Rats were injected with vincristine (VCR) at a dose of 4 mg/kg twice a week for 5 weeks. The VCR‐administered rats were divided into three groups and received saline, oxytocin, or liraglutide simultaneously with VCR. After the treatment period, electrophysiological, biochemical, histological, and immunohistochemical investigations were performed. Electromyography (EMG) recordings demonstrated significant alterations in the VCR + saline group (p < .001). Also, motor performance was decreased in the VCR + saline group (p < .05). Histologically, the axonal diameter was decreased in all groups. VCR + saline group showed significantly increased lipid peroxidation and decreased nerve growth factor (NGF) expression. However, the administration of oxytocin and liraglutide significantly prevented the EMG alterations, lipid peroxidation, and reduction in neuronal NGF expression. On the basis of these findings, oxytocin and liraglutide may be considered as potential agents for the prevention of VCR‐induced neuropathy.