Synthesis and antiprotozoal evaluation of benzothiazolopyrroloquinoxalinones,analogues of kuanoniamine A

Boc-aminoethylindoloquinone 8, a key intermediate for the building of pentacyclic quinoneimines, analogues of kuanoniamine A, was synthesized by alkylation of 4,7-dimethoxyindole 3 with 1,2-dibromoethane followed by transformation into azide, reduction of the latter with trimethylphosphine in the presence of 2-(tert-butoxycarbonyloximino)-2-phenylacetonitrile and oxydative demethylation of the Boc-amine 6 with silver(II) oxide. Quinone 8 was then treated in situ with the thiazole o-quinodimethane 10 to afford a regioisomeric mixture of the tetracyclic quinones 11. Treatment of the mixture with trifluoroacetic acid and molecular sieves 4-A provided the corresponding quinoneimines 12. Separation of the regioisomers was performed by preparative thin-layer chromatography on silica gel. The structural assignment was made by 2D 1H-13C HMBC correlations performed on the less polar regioisomer 12b. In vitro anti-leishmanial assays showed that the tested compounds possess a good potency towards two Leishmania sp. as well as against a virulent strain of Toxoplasma gondii and without any cytotoxicity against THP-1 cells.     

Effects of Barium Stress in <i>Brassica juncea</i> and <i>Cakile maritima</i>: The Indicator Role of Some Antioxidant Enzymes and Secondary Metabolites

Soil contamination by toxic trace metal elements, like barium (Ba), may stimulate various undesirable changes in the metabolic activity of plants. The plant responses are fast and with, direct or indirect, generation of reactive oxygen species (ROS). To cope with the stress imposed by the ROS production, plants developed a dual cellular system composed of enzymatic and non-enzymatic players that convert ROS, and their by-products, into stable nontoxic molecules. To assess the Ba stress response of two Brassicaceae species (Brassica juncea, a glycophyte, and Cakile maritime, a halophyte), plants were exposure to different Ba concentrations (0, 100, 200, 300 and 500 μM). The plants response was evaluated through their morphology and development, the determination of plant leaves antioxidant enzymatic activities and by the production of plants secondary metabolites. Results indicated that the two Brassicaceae species have the ability to survive in an environment containing Ba (even at 500 μM). The biomass production of C. maritima was slightly affected whereas an increase in biomass B. juncea was noticed. The stress imposed by Ba activated the antioxidant defense system in the two species, noticed by the changes in the leaves activity of catalase (CAT), ascorbate peroxidase (APX) and guaicol peroxidase (GPX), and of the secondary metabolites, through the production of total phenols and flavonoids. The enzymatic response was not similar within the two plant species: CAT and APX seem to have a more important role against the oxidative stress in C. maritima while in B. juncea is GPX. Overall, total phenols and flavonoids production was more significant in the plants aerial part than in the roots, of the both species. Although the two Brassicaceae species response was different, in both plants catalytic and non-catalytic transformation of ROS occurs, and both were able to overcome the Ba toxicity and prevent the cell damage.     

Plant peroxidases: biomarkers of metallic stress

The term “peroxidase” designs a group of hemoproteins with a wide structural variability. These enzymes catalyze the redox reaction between hydrogen peroxide and some reductors. They can be found in animals, plants and microorganisms. In plants, peroxidases are involved in numerous cellular processes such as development and stress responses. In fact, they are involved in growth regulation by controlling hormonal and cell wall metabolism and antioxidant defense. On the other hand, these enzymes are considered as a biomarker indicating biotic and abiotic stresses. Under metallic stress conditions, the quantitative and qualitative profiles of peroxidases are generally modified. Such modulations could prove the major role played by these enzymes in the defense mechanism. In this paper, we discussed the variation of isoperoxidases behavior under metallic stress conditions.     

Association between genome-wide association studies reported SNPs and pediatric-onset Crohn’s disease in Canadian children

A recent pediatric-focused genome-wide association study has implicated three novel susceptibility loci for Crohn’ disease (CD).We aimed to investigate whether the three recently reported and other previously reported genes/loci were also associated with CD in Canadian children. A case–control design was implemented at three pediatric gastroenterology clinics in Canada. Children <19 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in 19 reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. A total of 563 cases and 553 controls were studied. The mean (±SD) age of the cases was 12.3 (±3.2) years. Most cases were male (56.0%), had ileo-colonic disease (L3 ± L4, 48.8%) and inflammatory behavior (B1 ± p, 87.9%) at diagnosis. Allelic association analysis (two-tailed) showed that 8 of the 19 targeted SNPs were significantly associated with overall susceptibility for CD. Associations with one additional SNP was borderline non-significant. Significantly associated SNPs included SNPs rs1250550 (p = 0.026) and rs8049439 (p = 0.04), recently reported to be specifically associated with pediatric-onset CD.Based on the results, we confirmed associations between two of the three novel pediatric-CD loci and other regions reported for associations with either pediatric and/or adult-onset CD.     

An on-line technique for monitoring propionic acid fermentation

An on-line technique, based on measuring the increase in pressure due to CO₂ release in a closed air-tight reactor, was used to evaluate the fermentation of lactate by propionibacteria. The method was applied to batch cultures of Propionibacterium shermanii grown in yeast extract/sodium lactate medium containing lactate as a carbon source under micro-aerophilic conditions. Gas pressure evolution was compared both with substrate consumption and metabolites production and with acidification and growth. Linear relationships were found between gas pressure variation, lactate consumption and propionate and acetate production. The technique also enabled the evaluation of total CO₂ produced, by taking account of pressure, oxygen and pH measurements. These results tend to show that this simple and rapid method could be useful to monitor propionic acid bacteria growth.     

The first checklist of black fungus gnats (Diptera: Sciaridae) of Morocco

The first checklist of black fungus gnats is established; new faunistic records of Sciaridae are presented, providing a list of 10 genera and 55 species. Forty-eight species are newly listed for Morocco, increasing the total of Sciaridae known from Morocco to 69 species, belonging to 12 genera, of which six (Austrosciara Schmitz & Mjöberg, 1924, Bradysiopsis Tuomikoski, 1960, Epidapus Haliday, 1851, Lycoriella Frey, 1942, Pseudolycoriella Menzel & Mohrig, 1998 and Sciara Meigen, 1803) are newly reported for Moroccan fauna.     

Toward the smallest active subdomain of a TIM-barrel fold: insights from a truncated α-amylase

AmyTM is a truncated mutant of the α-amylase of Bacillus stearothermophilus US100. It has been derived from the wild type amylase gene via a reading frame shift, following a tandem duplication of the mutant primer, associated to an Adenine base deletion. AmyTM was composed of 720 nucleotides encoding 240 amino acid residues out of 549 of the wild type. The AmyTM protein was devoided of the three catalytic residues but still retains catalytic activity. It is Ca-independent maltotetraose producing amylase, optimally active at pH 6 and 60 °C, under monomeric or multimeric forms.AmyTM is the smallest functional truncated TIM barrel. It contains the βαβα unit as the minimal subdomain associated to an enzymatic function. The enzymatic activity can, until now, be attributed to the presence of the whole domain B, in the structure of AmyTM. This mutant revealed, for the first time, the regeneration of a catalytic site after its abolition. This fact may be considered as the restoration of a primitive active site, which was lost in the course of evolution toward more stable domains.     

Structural Changes of Cell Wall and Lignifying Enzymes Modulations in Bean Roots in Response to Copper Stress

Fourteen-day-old bean seedlings were cultured in nutrient solution containing Cu²⁺ ions at various concentrations (50 and 75 μM of CuSO₄) for 3 days. This excess of copper induced a reduction in the water volume absorbed by the plants. Moreover, this reduction was accompanied by an increase of the amount of copper taken up by the roots. Analysis by native gel electrophoresis of cell wall peroxidase activities in the roots revealed a stimulation of two anionic isoforms (A₂ and A₃) under cupric stress conditions. Moreover, the activity of phenylalanine ammonia lyase (EC. 4.3.1.5), which plays an important role in plant defense, was enhanced. Copper-treated bean roots showed modifications in the cell walls of various tissues. Label for lignin, callose, and suberin with berberine-aniline blue revealed abnormal cell wall thickenings in the endodermis, the phloem, and the xylem, especially in plants treated with 75 μM CuSO₄.