Understanding the binding interaction between phenyl boronic acid P1 and sugars: determination of association and dissociation constants using S–V plots,steady‐state spectroscopic methods and molecular docking

Continuous monitoring of glucose and sugar sensing plays a vital role in diabetes control. The drawbacks of the present enzyme‐based sugar sensors have encouraged the investigation into alternate approaches to design new sensors. The popularity of fluorescence sensors is due to their ability to bind reversibly to compounds containing diol. In this study we investigated the binding ability of phenyl boronic acid P1 for monosaccharides and disaccharides (sugars) in aqueous medium at physiological pH 7.4 using steady‐state fluorescence and absorbance. P1 fluorescence was quenched due to formation of esters with sugars. Absorbance and fluorescence measurements led to results that indicated that the sugars studied could be ordered in terms of their affinity to P1, as stated: sucrose > lactose > galactose > xylose > ribose > arabinose. In each case, the slope of modified Stern–Volmer plots was nearly 1, indicating the presence of only a single binding site in boronic acids for sugars. Docking studies were carried out using Schrodinger Maestro v.11.2 software. The binding affinity of phenyl boronic acid P1 with periplasmic protein (PDB ID 2IPM and 2IPL) was estimated using GlideScore.     

Deoxypreussomerins from Jatropha curcas: are they also plant metabolites?

Three deoxypreussomerins, palmarumycins CP1, JC1 and JC2, have been isolated from a collection of the stems of Jatropha curcas. The second and third compounds are antibacterial constituents which were characterized from spectral evidence. The X-ray crystallographic structure of palmarumycin JC1 was also studied. Deoxypreussomerins have been obtained here from a plant source in appreciable quantities.     

Sodium-independent low-affinity D-glucose transport by human sodium/D-glucose cotransporter 1: critical role of tryptophan 561

Although there is no evidence of significant Na-independent glucose flux in tissues naturally expressing SGLT1, previous kinetic and biophysical studies suggest that sodium/d-glucose cotransporter 1 (hSGLT1) can facilitate sodium-independent d-glucose transport and may contain more than one sugar binding site. In this work, we analyze the kinetic properties and conformational states of isolated hSGLT1 reconstituted in liposomes by transport and fluorescence studies in the absence of sodium. In the transport studies with hSGLT1, significant sodium-independent phlorizin inhibitable alpha-methyl d-glucopyranoside (alpha-MDG) uptake was observed which amounted to approximately 20% of the uptake observed in the presence of a sodium gradient. The apparent affinity constant for alpha-MDG was thereby 3.4 +/- 0.5 mM, a value approximately 10-fold higher than that in the presence of sodium. In the absence of sodium, various sugars significantly decreased the intrinsic Trp fluorescence of hSGLT1 in proteoliposomes exhibiting the following sequence of affinities: alpha-MDG > d-glucose approximately d-galactose > 6-deoxy-d-glucose > 2-deoxy-d-glucose > d-allose. Furthermore, significant protection effects of d-glucose or phlorizin against potassium iodide, acrylamide, or trichloroethanol quenching were observed. To locate the Trps involved in this reaction, we generated mutants in which all Trps were sequentially substituted with Phe. None of the replacements significantly affected sodium-dependent uptake. Uptake in the absence of sodium and typical fluorescence changes depended, however, on the presence of Trp at position 561. This Trp residue is conserved in all known SGLT1 forms (except Vibrio parahaemolyticus SGLT) and all SGLT isoforms in humans (except hSGLT3). If all these data are taken into consideration, it seems that Trp-561 in hSGLT1 forms part of a low-affinity sodium-independent binding and/or translocation site for d-glucose. The rate of sodium-independent translocation via hSGLT1 seems, however, to be tightly regulated in the intact cell by yet unknown factors.     

Isolation and Characterization of Pediocin NV 5 Producing <Emphasis Type="Italic">Pediococcus acidilactici</Emphasis> LAB 5 from Vacuum-Packed Fermented Meat Product

A potentially novel antimicrobial compound producing Pediococcus acidilactici LAB 5 was isolated from vacuum-packed fermented meat product. This compound was found active against some species of Enterococcus, Leuconostoc, Staphylococcus and Listeria, many of which are associated with food spoilage and food related health hazards. The strain was found to be a paired cocci which can utilize a broad range of carbohydrates and produce acid identical to the P. acidilactici and P. pentoseus. Since the antimicrobial agent was sensitive to proteolytic enzymes but quite resistant to heat, it was identified as a bacteriocin and was designated as Pediocin NV 5. The molecular weight of the bacteriocin was 10.3 kDa and the bacterium possessed a 5 kbp plasmid responsible for bacteriocin production and also for vancomycin resistance phenotype.     

Arbuscular mycorrhizal fungi and biochar improves drought tolerance in chickpea

Arbuscular mycorrhizal fungi (AMF) inoculation and biochar amendment has been reported to improve growth of several crop plants however their role in stress amelioration individually as well as in combination has not been worked out. This experiment was conducted to evaluate the application of AMF and biochar on the performance of chickpea under drought stress. The treatments included the individual as well as combined treatment of AMF and biochar to drought stressed and normal chickpea plants. Plants inoculation improved growth in terms of shoot and root length, leaf area and number of branches which was observed to show a steep decline due to drought stress. Drought declined the AMF colonization potential though biochar amendment ameliorated the negative effects of drought significantly by improving the spore population, number of mycelium, vesicle and arbuscules and the percentage of colonization as well. Increased chlorophyll synthesis in biochar and AMF treated plants was obvious, which lead to significant enhancement in the net photosynthetic efficiency. Drought stress also declined the relative water content (RWC) and membrane stability index (MSI), while treatment of biochar and AMF either individually or in combination mitigated the deleterious effects to considerable extent and caused a significant enhancement in RWC and MSI under normal conditions. Amendments with biochar and AMF inoculation increased the nitrogen fixation attributes including the number and weight of nodules, leghemoglobin content and activity of nitrate reductase enzyme leading to greater uptake and assimilation of nitrogen in them when compared to drought stressed plants. Drought stressed chickpea plants exhibited considerable reduction in uptake of nitrogen and phosphorous which was ameliorated by biochar and AMF treatments. It could be suggested that increase in growth and physiological attributes in chickpea due to biochar amendments and AMF inoculation under drought stress were plausibly due to their involvement in nitrogen and phosphorous uptake, chlorophyll synthesis and photosynthesis.     

Autophagy triggered by magnolol derivative negatively regulates angiogenesis

Angiogenesis has a key role in the tumor progression and metastasis; targeting endothelial cell proliferation has emerged as a promising therapeutic strategy for the prevention of cancer. Previous studies have revealed a complex association between the process of angiogenesis and autophagy and its outcome on tumorigenesis. Autophagy, also known as type-II cell death, has been identified as an alternative way of cell killing in apoptotic-resistant cancer cells. However, its involvement in chemoresistance and tumor promotion is also well known. In this study, we used a derivate of natural product magnolol (Ery5), a potent autophagy inducer, to study the association between the autophagy and angiogenesis in both in vitro and in vivo model system. We found that the robust autophagy triggered by Ery5, inhibited angiogenesis and caused cell death independent of the apoptosis in human umbilical cord vein endothelial cells and PC-3 cells. Ery5 induced autophagy effectively inhibited cell proliferation, migration, invasion and tube formation. We further demonstrated that Ery5-mediated autophagy and subsequent inhibition of angiogenesis was reversed when autophagy was inhibited through 3-methyl adenine and knocking down of key autophagy proteins ATG7 and microtubule-associated protein light chain 3. While evaluating the negative regulation of autophagy on angiogenesis, it was interesting to find that angiogenic environment produced by the treatment of VEGF and CoCl2 remarkably downregulated the autophagy and autophagic cell death induced by Ery5. These studies, while disclosing the vital role of autophagy in the regulation of angiogenesis, also suggest that the potent modulators of autophagy can lead to the development of effective therapeutics in apoptosis-resistant cancer.     

Synthesis and biological evaluation of trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxyalkylamine derivatives against drug susceptible,non-replicating M. tuberculosis H37Rv and clinical multidrug resistant strains

Synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of Mycobacterium tuberculosis have been reported. All the new compounds in the series exhibited MIC between 1.56 and 6.25 μg/ml. Two compounds 1i and 1j with low MIC and low cytotoxicity showed significant reduction in CFU in infected mouse macrophages at 1× MIC concentration. The compound 1i inhibited the growth of M. tuberculosis in mice at 100 mg/kg dose with 1.35 log₁₀ reduction of CFU in lungs tissue and was active against non-replicating Mycobacterium tuberculosis under anaerobic condition.