S-glycosides in medicinal chemistry: Novel synthesis of cyanoethylene thioglycosides and their pyrazole derivatives

A one-pot reaction of a sodium 2-cyanoethylene-1-thiolate salt with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides affords a new class of cyanoethylene thioglycosides. The conversion to the corresponding 5-aminopyrazoles confirms the E-configuration of these cyanoethylene thioglycosides.     

Differential vascular actions of ethanol in feline middle cerebral and mesenteric artery.

The vascular actions of ethanol on feline middle cerebral and mesenteric arteries were investigated in vitro. Ethanol (20-500 mM) caused potent contraction in cerebral arteries, but it contracted the mesenteric arteries only weakly. In the middle cerebral artery (but not in the mesenteric artery) ethanol (300 mM) potentiated the noradrenaline (5.10(-6) M) induced contractions. Antiserum for endothelin (in an appropriate concentration to inhibit endothelin-induced contraction; 0.02 mg/ml) did not inhibit the ethanol-induced contractions. Endothelium-dependent relaxations induced by acetylcholine and ATP were also affected by ethanol (300 mM); in the cerebral artery acetylcholine- but not ATP-induced relaxations, whereas in the mesenteric artery ATP- but not acetylcholine-induced relaxations were inhibited significantly. The results suggest that ethanol causes strong (endothelin-independent) contraction and facilitates the response to noradrenaline in the middle cerebral, but not in the mesenteric artery; and it selectively inhibits endothelium-dependent relaxation. These actions of ethanol may contribute to the development of vascular diseases.     

Melanogenesis Inhibitors from the Endophytic Fungus Aspergillus amstelodami

Two new compounds, named 3,4‐dimethoxyphenyl α‐d ‐ribofuranoside ( 1 ) and 3β‐(β‐d ‐glucopyranosyloxy)olean‐12‐ene‐23,28,30‐trioic acid ( 2 ), together with thirteen known compounds, were isolated from the white beans culture of the marine derived endophytic fungus Aspergillus amstelodami. Structure elucidation of the new compounds was carried out by one‐, two‐dimensional spectroscopy, and high resolution electrospray ionization mass. The antimelanogenic and anti‐allergic activity of the isolated compounds were investigated. Compounds 4 , 7 , 1 , 3 , 11 , 6 and 9 selectively suppressed melanin production in B16 melanoma cells, using arbutin as a positive control. Their IC₅₀ values were 30.8±5.57, 38.5±6.08, 52.6±6.64, 98.0±1.16, 100.4±3.05, 112.0±0.22 and 144.7±2.35 μm , respectively, while that of arbutin was 151.7±1.27 μm . The tested compounds did not show any significant anti‐allergic activity in RBL‐2H3 cells, as compared to quercetin.     

Antihyperlipidemic and antioxidant effects of feather protein hydrolysate in high‐fat diet‐fed mice

The hyperlipidemia is a serious health problem that increases the risk of many complications including cardiovascular disease. This study aims to evaluate the possible antihyperlipidemic effects of the feather protein hydrolysate (FPH) in a mice fed with a high‐fat diet (HFD)‐fed mice during 5 weeks. The FPH administration improved dose‐dependent lipid profile, as well as the liver and renal dysfunction indices in hyperlipidemic mice. The FPH also restored the antioxidant status in liver, kidney, and heart by lowering the lipid peroxidation and enhancing the antioxidant enzymes (catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase [SOD]). Moreover, the histological studies proved that FPH administration prevents hepatic steatosis, glomerular hyperfiltration risk, and cardiac muscle hypertrophy. Accordingly, the FPH is a promising novel medicinal ingredient for possible use in the hyperlipidemic treatment and related complications.     

Chlorzoxazone esters of some non-steroidal anti-inflammatory (NSAI) carboxylic acids as mutual prodrugs: Design,synthesis, pharmacological investigations and docking studies

The discovery of the inducible isoform of cyclooxygenase enzyme (COX-2) spurred the search for anti-inflammatory agents devoid of the undesirable effects associated with classical NSAIDs. New chlorzoxazone ester prodrugs (6–8) of some acidic NSAIDs (1–3) were designed, synthesized and evaluated as mutual prodrugs with the aim of improving the therapeutic potency and retard the adverse effects of gastrointestinal origin. The structure of the synthesized mutual ester prodrugs (6–8) were confirmed by IR, ¹H NMR, mass spectroscopy (MS) and their purity was ascertained by TLC and elemental analyses. In vitro chemical stability revealed that the synthesized ester prodrugs (6–8) are chemically stable in hydrochloric acid buffer pH 1.2 as a non-enzymatic simulated gastric fluid (SGF) and in phosphate buffer pH 7.4 as non-enzymatic simulated intestinal fluid (SIF). In 80% human plasma, the mutual prodrugs were found to be susceptible to enzymatic hydrolysis at relatively faster rate (t_1/2 ≈ 37 and 34 min for prodrugs 6 and 7, respectively). Mutual ester prodrugs (6–8) were evaluated for their anti-inflammatory and muscle relaxation activities. Scanning electromicrographs of the stomach showed that the ester prodrugs induced very little irritancy in the gastric mucosa of rats after oral administration for 4 days. In addition, docking of the mutual ester prodrugs (6–8) into COX-2 active site was conducted in order to predict the affinity and orientation of these prodrugs at the enzyme active site.     

GC-MS SPME profiling of rhizobacterial volatiles reveals prospective inducers of growth promotion and induced systemic resistance in plants

Chemical and plant growth studies of Bacilli strains GB03 and IN937a revealed that the volatile components 2,3-butanediol and acetoin trigger plant growth promotion in Arabidopsis. Differences in growth promotion when cytokinin-signaling mutants are exposed to GB03 versus IN937a volatiles suggest a divergence in chemical signaling for these two bacterial strains. To provide a comprehensive chemical profile of bacterial volatiles emitted from these biologically active strains, headspace solid phase microextraction (SPME) coupled with software extraction of overlapping GC-separated components was employed. Ten volatile metabolites already reported from GB03 and IN937a were identified as well as 28 compounds not previously characterized. Most of the newly identified compounds were branched-chain alcohols released from IN937a, at much higher levels than in GB03. Principal component analysis clearly separated GB03 from IN937a, with GB03 producing higher amounts of 3-methyl-1-butanol, 2-methyl-1-butanol and butane-1-methoxy-3-methyl. The branched-chain alcohols share a similar functional motif to that of 2,3-butanediol and may afford alternative structural patterns for elicitors from bacterial sources.     

Photosynthetic based algal-bacterial combined treatment of mixtures of organic pollutants and CO2 mitigation in a continuous photobioreactor

An algal-bacterial microcosm was synthetically constructed of Chlorella vulgaris MMl and Pseudomonas MTl. This microcosm was able to treat simulated wastewater supplemented with mixtures of phenol and pyridine up to 4.6 and 4.4 mM, respectively, in a continuous stirred tank bioreactor (CSTR) using photosynthetic oxygenation. Complete pollutant removal and detoxification and 82 % removal of introduced chemical oxygen demand (COD) were achieved at a hydraulic retention time (HRT) of 2.7 days. Increasing the influent load to 5.3 and 6.3 mM reduced the removal of phenol, pyridine and COD to 78, 21 and 59 %, respectively. Fertilization of the photobioreactor with 24 mM NaHCO₃ restored the treatment and detoxification efficiencies. The system was able to additionally mitigate up to 72 mM NaHCO₃ at the same HRT. Although the fertilization increased the system treatment efficiency, the settleability of the algal-bacterial microcosm was significantly reduced. When the photobioreactor was operated at HRT of 2.7 days in a 12/12 h of dark/light cycle, complete removal of 4.7 mM phenol was recorded but only 11 % of 5.7 mM pyridine was removed. The COD removal efficiency and CO₂ mitigation were also reduced to 65 and 86 %, respectively, and the effluent retained significant toxicity where 73 % inhibition was recorded. Elongation of the illumination time to 48 h (HRT of 4 days at 12/12 h dark/light cycle) restored the treatment and detoxification efficiencies.     

Cloning, expression and functional activity of deoxyhypusine synthase from Plasmodium vivax

Background  

Plasmodium vivax is the most widespread human malaria parasite. However, genetic information about its pathogenesis is limited at present, due to the lack of a reproducible in vitro cultivation method. Sequencing of the Plasmodium vivax genome suggested the presence of a homolog of deoxyhypusine synthase (DHS) from P. falciparum, the key regulatory enzyme in the first committed step of hypusine biosynthesis. DHS is involved in cell proliferation, and thus a valuable drug target for the human malaria parasite P. falciparum. A comparison of the enzymatic properties of the DHS enzymes between the benign and severe Plasmodium species should contribute to our understanding of the differences in pathogenicity and phylogeny of both malaria parasites.