Identification of a Bacteria-produced Benzisoxazole with Antibiotic Activity against Multi-drug Resistant Acinetobacter baumannii

The emergence of multi-drug resistant pathogenic bacteria represents a serious and growing threat to national healthcare systems. Most pressing is an immediate need for the development of novel antibacterial agents to treat Gram-negative multi-drug resistant infections, including the opportunistic, hospital-derived pathogen, Acinetobacter baumannii. Herein we report a naturally occurring 1,2-benzisoxazole with minimum inhibitory concentrations as low as 6.25 μg ml−1 against clinical strains of multi-drug resistant A. baumannii and investigate its possible mechanisms of action. This molecule represents a new chemotype for antibacterial agents against A. baumannii and is easily accessed in two steps via de novo synthesis. In vitro testing of structural analogs suggest that the natural compound may already be optimized for activity against this pathogen. Our results demonstrate that supplementation of 4-hydroxybenzoate in minimal media was able to reverse 1,2-benzisoxazole’s antibacterial effects in A. baumannii. A search of metabolic pathways involving 4-hydroxybenzoate coupled with molecular modeling studies implicates two enzymes, chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyltransferase, as promising leads for the target of 3,6-dihydroxy-1,2-benzisoxazole

Forced, not voluntary, exercise effectively induces neuroprotection in stroke

Previous treadmill exercise studies showing neuroprotective effects have raised questions as to whether exercise or the stress related to it may be key etiologic factors. In this study, we examined different exercise regimens (forced and voluntary exercise) and compared them with the effect of stress-only on stroke protection. Adult male Sprague-Dawley rats (n = 65) were randomly assigned to treatment groups for 3 weeks. These groups included control, treadmill exercise, voluntary running wheel exercise, restraint, and electric shock. Levels of the stress hormone, corticosterone, were measured in the different groups using ELISA. Animals from each group were then subjected to stroke induced by a 2-h middle cerebral artery (MCA) occlusion followed by 48-h reperfusion. Infarct volume was determined in each group, while changes in gene expression of stress-induced heat shock proteins (Hsp) 27 and 70 were compared using real-time PCR between voluntary and treadmill exercise groups. The level of corticosterone was significantly higher in both stress (P < 0.05) and treadmill exercise (P < 0.05) groups, but not in the voluntary exercise group. Infarct volume was significantly reduced (P < 0.01) following stroke in rats exercised on a treadmill. However, the amelioration of damage was not duplicated in voluntary exercise, even though running distance in the voluntary exercise group was significantly (P < 0.01) longer than that of the forced exercise group (4,828 vs. 900 m). Furthermore, rats in the electric shock group displayed a significantly increased (P < 0.01) infarct volume. Expression of both Hsp 27 and Hsp 70 mRNA was significantly increased (P < 0.01) in the treadmill exercise group as compared with that in the voluntary exercise group. These results suggest that exercise with a stressful component, rather than either voluntary exercise or stress alone, is better able to reduce infarct volume. This exercise-induced neuroprotection may be attributable to up-regulation of stress-induced heat shock proteins 27 and 70

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Not AvailableThere is a shred of evidence to suggest that Emblica officinalis Gaertn, the botanical name for amla seeds, has greater medicinal potential than amla fruit. We conducted this work to assess the anti-inflammatory, antibacterial, and antioxidant capacities of E. officinalis seed extracts. The bioactive components from the seeds were fractionated using chloroform, hexane, methanol, and diethyl ether, according to the polarity of the solvents. The total amount of phenolic and flavonoid was estimated. Both the reducing power and antioxidant capacities of the extracts were evaluated using the DPPH (1,1-diphenyl-2-picryl-hydrazyl) technique. 15-lipoxygenase (LOX) was inhibited by seed extracts at doses ranging from 5 to 25 micrograms. In silico docking was employed to assess the results. Some human pathogenic microorganisms were tested for their antibacterial activity using the agar disc diffusion method. Escherichia coli, Proteus vulgaris, and Klebsiella pneumonia were inhibited by a methanolic extract with an IC50 value of 58g, making it the most common organic solvent extract. Methanolic extracts also showed good antioxidant and antibacterial activity. Our investigation led us to discover that amla seeds have anti-inflammatory, antioxidant, and antibacterial effectsNot Availabl

Synthesis of triazolylmethyl-linked nucleoside analogs via combination of azidofuranoses with propargylated nucleobases and study on their cytotoxicity

KARAYILDIRIM, Tamer/0000-0001-7451-0810; HALAY, Erkan/0000-0002-0084-7709WOS: 000429350900009Copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition reactions (CuAAC) between azidofuranoses and propargyl-nucleobases were carried out in the presence of CuSO4 center dot 5H(2)O and sodium ascorbate as catalytic system to provide the corresponding 1,4-disubstituted-1,2,3-triazole-bridged nucleoside analogs in good yields. Twelve new sugar-based triazolylmethyl-linked nucleoside analogs were synthesized and screened for their cytotoxic activity against MDA-MB-231, Hep3B, PC-3, SH-SY5Y, and HCT-116 cancer cell lines and control cell line (L929). Most of the compounds were moderately effective against all the cancer cell lines assayed. Particularly, among the tested compounds, 1,2,3-triazole-linked 5-fluorouracil-mannofuranose hybrid was found to be the most potent cytotoxic agent against HCT-116, Hep3B, SH-SY5Y cells with IC50 values of 35.6, 71.1, and 75.6 mu M, respectively. None of the triazolylmethyl-linked nucleoside analogs exhibited cytotoxic effect against the control cells L929.TUBITAK-Research Council of Turkey [114Z757]; TUBITAK-BIDEBTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [2211A]This work was supported by TUBITAK-Research Council of Turkey with the project number 114Z757. Author E. Halay also offers his profound thanks to TUBITAK-BIDEB 2211A for their bursary support

Chemical changes in detrital matter upon digestive processes in a sesarmid crab feeding on mangrove leaf litter

Pathways and rates of decomposition of detrital matter partly depend on its chemical composition. Digestive processes of detritivores drive changes in the chemical composition of detritus, and these changes translate into the chemical composition of the organic matter sequestered into soils and sediments. The latter, in turn, determines how stable organic matter stocks are towards further decay and release of climate-active gases thereupon. We used metabolic fingerprinting to monitor changes in the chemical composition of mangrove detritus upon digestion by a mangrove crab. According to analyses through pyrolysis-GC/MS, the decaying leaf litter of three mangrove species of the Indo-West Pacific, Bruguiera gymnorhiza (L.) Savigny ex Lam. and Poiret 1798, Ceriops tagal (Perr.) C.B. Robinson 1908, and Rhizophora mucronata Lam. 1804, clearly differed from each other in their chemical signature. The feces of detritivorous crabs (Sesarma bidens de Haan 1835) feeding on these detrital sources differed from the source litter in their chemical composition, obviously owing to digestive processes. However, the chemical signatures of feces were more similar to those of their source litter than to those of feces from different litter sources, indicating that the origin of organic matter can be tracked in fecal material. Moreover, male and female crabs appear to exhibit sex-specific digestive processes, as they produced feces that clearly differed from each other in their chemical signature. The 15 chemical compounds most relevant for distinguishing litter sources and fecal material provide first hints on which compounds discriminate the different tree species and characterize digestion by S. bidens. For instance, coumaran (dihydro-benzofuran), indicative of certain carbohydrates, was abundant as a pyrolysis product of the litter of R. mucronata and, to a much lesser degree, C. tagal. Hence, the carbohydrates that were pyrolysed into coumaran seem to discriminate the former two litter sources. Similarly, a pyrolysis-derivate of plant phenolics or proteins, discriminated C. tagal from the other litter sources. From this, we conclude that even subtle differences in litter chemistry and digestive processes of detritivores can be characterized and followed with high resolution through (py-)GC/MS. Further, we propose that the origin of fecal material can be identified with the aid of this technique, and we are currently studying whether the origin of organic matter in the sediment can also be inferred from (py-)GC/MS-data.info:eu-repo/semantics/publishedVersio