Regioselectivity in the glycosylation of 5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-thiol

The glycosylation of 5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-thiol (1) and its 3-benzylsulfanyl and 3-methylsulfanyl derivatives with different glycosyl halides 2-4 has been studied in presence of base. The S-glycosides 5-7 were obtained in the presence of triethylamine, whereas the respective S,N⁴-bis(glycosyl) derivatives 8-10 were synthesized in the presence of potassium carbonate; the S,N²-bis(glycosyl) isomer 11 could also be isolated in the case of the galactosyl analog. Similarly, after protecting 1 as 3-benzyl(methyl)sulfanyl derivatives 12 or 13, the N⁴-glycosyl analogs 14-19 as well as minor amounts of S,N²-bis(galactosyl) isomers 20 and 21 were formed. The theoretical calculations using AM1 semiempirical methods agreed with the experimental results. Microwave irradiation (MWI) led to higher yields in much less time than the conventional methods, and no change in regioselectivity has been noticed.     

Novel thermostable lipase from <Emphasis Type="Italic">Bacillus circulans</Emphasis> IIIB153: comparison with the mesostable homologue at sequence and structure level

Thermophilic Bacillus circulans IIIB153 isolated from hot springs of North West Himalayas, India, produced an extracellular lipase, which exhibited significant biofilm disruption property on the static biofilm disruption model with a single species of Actinomyces viscosous. The gene encoding the lipase was cloned and overexpressed in Escherichia coli. Recombinant Bacillus circulans lipase (BCL), a monomer with molecular mass of 43 kDa also exhibited significant biofilm disruption activity. The enzyme was optimally active at 60°C, pH 8.5 and retained >70% of its original activity after 1 h incubation at 60°C. 3D structure of BCL developed by homology modeling showed a typical α/β hydrolase fold, a characteristic feature of lipolytic enzymes. Comparison of thermostable BCL with mesostable lipase from Chromobacterium viscosum at the sequence and structure level showed distinct variations in the structural features, with the presence of a high content of proline residues, aromatic amino acids and salt bridges. These features along with the presence of zinc-binding site observed in BCL structure could have a potential role in thermal stability of the enzyme.     

Trehalose administration attenuates atherosclerosis in rabbits fed a high-fat diet

Disruption of macrophage autophagy is a major contributor to macrophage dysfunction and subsequent inflammation leading to atherosclerosis. Trehalose is a natural disaccharide that is able to induce macrophage autophagy-lysosomal biogenesis and reduce inflammation. Here, we studied the efficacy of intravenous trehalose administration in reducing atherosclerotic plaque burden in high-cholesterol-fed rabbits. Adult male New Zealand white Rabbits were fed with a high-fat diet containing 1% cholesterol for 8 weeks followed by a cholesterol-free diet for the next 4 weeks. In the latter 4-week phase of the cholesterol-free diet, one group received intravenous trehalose solution at a dose of 350 mg/kg, three times per week. In the control group, an equivalent volume of PBS (3 mL) was administered with the same protocol. At the end of the 12th week of the study, all rabbits were anesthetized and aortic arch sections were collected followed by hematoxylin and eosin staining and assessment of plaque grading. Fasting serum lipids were also measured using routine enzymatic methods. At the end of the 12th week, there were no significant differences in the body weight and blood lipids between the control- and trehalose-treated groups. Intravenous trehalose administration significantly attenuated atherosclerotic plaque development as revealed by reduced plaque grading ( P = 0.048) and intima/media thickness ratio ( P = 0.017). Intimal thickening was also found to be reduced in the trehalose versus control group, though this reduction did not reach statistical significance. The present study provided evidence as to the efficacy of short-term intravenous trehalose administration in regressing atherosclerotic plaque in high-fat-fed rabbits.     

Brick by brick: metabolism and tumor cell growth

Tumor cells display increased metabolic autonomy in comparison to non-transformed cells, taking up nutrients and metabolizing them in pathways that support growth and proliferation. Classical work in tumor cell metabolism focused on bioenergetics, particularly enhanced glycolysis and suppressed oxidative phosphorylation (the 'Warburg effect'). But the biosynthetic activities required to create daughter cells are equally important for tumor growth, and recent studies are now bringing these pathways into focus. In this review, we discuss how tumor cells achieve high rates of nucleotide and fatty acid synthesis, how oncogenes and tumor suppressors influence these activities, and how glutamine metabolism enables macromolecular synthesis in proliferating cells.     

Effect of Al, Co, and Pb ions on growth ofFrankia spp. in a mineral medium

Growth of three Frankia strains associated with roots of Casuarina tree, treated with different concentrations of metal ions, was measured as total protein content. One strain was highly resistant to different aluminum ion concentrations up to 10 mmol/L. The other two strains were more sensitive to the higher aluminum concentrations (1.25-10 mmol/L). Growth inhibition by cobalt and lead concentrations varied, depending on the tested strain. Stimulation occurred only at cobalt concentrations of 0.33 and 0.65 mmol/L for one strain.     

Novel pyrrolopyrimidine derivatives: design,synthesis, molecular docking,molecular simulations and biological evaluations as antioxidant and anti-inflammatory agents

Current medical approaches to control the Covid-19 pandemic are either to directly target the SARS-CoV-2 via innovate a defined drug and a safe vaccine or indirectly target the medical complications of the virus. One of the indirect strategies for fighting this virus has been mainly dependent on using anti‐inflammatory drugs to control cytokines storm responsible for severe health complications. We revealed the discovery of novel fused pyrrolopyrimidine derivatives as promising antioxidant and anti-inflammatory agents. The newly synthesised compounds were evaluated for their in vitro anti-inflammatory activity using RAW264.7 cells after stimulation with lipopolysaccharides (LPS). The results revealed that 3a, 4b, and 8e were the most potent analogues. Molecular docking and simulations of these compounds against COX-2, TLR-2 and TLR-4 respectively was performed. The former results were in line with the biological data and proved that 3a, 4b and 8e have potential antioxidant and anti-inflammatory effects.     

Products of the Escherichia coli acid fitness island attenuate metabolite stress at extremely low pH and mediate a cell density-dependent acid resistance

Escherichia coli has an ability, rare among the Enterobacteriaceae, to survive extreme acid stress under various host (e.g., human stomach) and nonhost (e.g., apple cider) conditions. Previous microarray studies have exposed a cluster of 12 genes at 79 centisomes collectively called an acid fitness island (AFI). Four AFI genes, gadA, gadX, gadW, and gadE, were already known to be involved in an acid resistance system that consumes an intracellular proton through the decarboxylation of glutamic acid. However, roles for the other eight AFI gene products were either unknown or subject to conflicting findings. Two new aspects of acid resistance are described that require participation of five of the remaining eight AFI genes. YhiF (a putative regulatory protein), lipoprotein Slp, and the periplasmic chaperone HdeA protected E. coli from organic acid metabolites produced during fermentation once the external pH was reduced to pH 2.5. HdeA appears to handle protein damage caused when protonated organic acids diffuse into the cell and dissociate, thereby decreasing internal pH. In contrast, YhiF- and Slp-dependent systems appear to counter the effects of the organic acids themselves, specifically succinate, lactate, and formate, but not acetate. A second phenomenon was defined by two other AFI genes, yhiD and hdeD, encoding putative membrane proteins. These proteins participate in an acid resistance mechanism exhibited only at high cell densities (>10(8) CFU per ml). Density-dependent acid resistance does not require any demonstrable secreted factor and may involve cell contact-dependent activation. These findings further define the complex physiology of E. coli acid resistance.     

Agricultural diversification: the potential for underutilised crops in Africa's changing climates.

Two of the greatest challenges currently facing humanity are the potential consequences of climate change and the actual consequences of reduced agricultural diversity. This paper considers the consequences of both climate change and reduced agricultural diversity on global food security and nutrition. The inextricable link between climate change and crop diversity is examined, particularly in the context of crop production in Africa where most agricultural diversity exists and where climate change will have most impact. The Green Revolution, often seen as a model for increasing global agricultural productivity, is reconsidered in terms of its failure to make a significant impact in hostile tropical environments such as those of much of Africa. An alternative or, at least, a complementary strategy, is advocated where we might better harness the huge repository of indigenous plant species cultivated and conserved by local communities for many generations across variable climates. An example is given of multidisciplinary research on bambara groundnut (Vigna subterranea), an ancient grain legume grown, cooked, processed and traded mainly by subsistence women farmers in sub-Saharan Africa. The experience gained on bambara groundnut is considered as a basis for similar efforts on many other potentially useful underutilised food crops in the climates of the future.     

Acyclo C-Nucleoside Analogs. Regioselective Annellation of a Triazole Ring to 5-Methyl-1,2,4-Triazino[5,6-b]Indole and Formation of Certain 3-Poly Hydroxyalkyl Derivatives

ABSTRACT

Cyclodehydrogenation of the ethylidene derivative of (5-methyl-1,2,4-triazino[5,6-b]indol-3-yl)hydrazine (1) gave the angular isomer, 1,10-dimethyl-1,2,4-triazolo[3′,4′:3,4][1,2,4]triazino[5,6-b]indole (4). The linear isomer, 3,10-dimethyl-1,2,4-triazolo[4′,3′:2,3][1,2,4]triazino[5,6-b]indole (7) could be prepared regioselectively by the cyclodehydration of the acetyl derivative of 1. The cyclodehydrogenation was extended to the monosaccharide derivatives of 1. The role of the N-methyl group on the site of annellation has been discussed.