Syntheses and biological activities of chalcone and 1,5-benzothiazepine derivatives: promising new free-radical scavengers, and esterase, urease, and alpha-glucosidase inhibitors

A series of 2,4-diaryl-2,3,4,5-tetrahydro- (36-40) and 2,4-diaryl-2,3-dihydro-1,5-benzothiazepines (25-35) have been synthesized from the corresponding chalcones 1-24. Both the benzothiazepines and chalcones were evaluated as DPPH free-radical scavengers and as inhibitors of cholinesterases, urease, and alpha-glucosidase. Compounds 2, 5, 6, 7, 10, 13, 18, 21, 36a, 37a, 37b, and 39a showed significant cholinesterase inhibiting activities. Among the 15 dihydro-1,5-benzothiazepines, 26, 32, and 35 exhibited significant radical-scavenging activities; and six tetrahydro-1,5-benzothiazepines (35, 36a, 36b, 37a, 37b, and 39a) were found to be inhibitors of AChE and BChE. Compounds 22, 25, 26, 33, 35, 36a, 37b, and 39a inhibited urease, and 25 and 27-31 were found to be potent inhibitors of alpha-glucosidase.     

A new Bacillus pasteurii urease inhibitor from Euphorbia decipiens

Inhibition of Bacillus pasteurii urease enzyme by 3,7,15-tri-O-acetyl-5-O-nicotinoyl-13,14-dihydroxymyrsinol (1), a diterpene ester with a myrsinol-type skeleton, isolated from Euphorbia decipiens Boiss. and Buhse, was un-competitive consistent with the molecular docking results. The Ki value was 117.40 +/- 0.7 microM.     

ALLELOPATHIC INHIBITION OF NITRIFICATION AND NITRIFYING BACTERIA IN A PONDEROSA PINE (PINUS PONDEROSA DOUGL.) COMMUNITY

The dynamics of ponderosa pine (Pinus ponderosa Dougl.) stands in western North Dakota were studied to determine the influence of plant-produced chemicals on nitrification rates and competitive interactions within the stands. Ponderosa pine accounted for more than 98% of all tree and shrub stratum stems in this climax community. Low levels of nitrate-nitrogen relative to ammonium-nitrogen and low numbers of Nitrosomonas and Nitrobacter in the soils indicated that nitrification rates were low. Inhibition of nitrification is often attributed to low soil pH in coniferous forests, but the slightly alkaline soils in this study (pH 7.25–7.75) suggested that another factor caused the low nitrification. Evidence obtained suggested that the reduction in nitrate synthesis was due to the production and subsequent transfer to the soil of secondary plant chemicals that were toxic to Nitrosomonas. Chemical inhibitors of nitrification, including caffeic acid, chlorogenic acid, quercitin, and condensed tannins, were found in extracts from ponderosa pine needles, bark, and A horizon soils. These extracts proved to be toxic to soil suspensions of Nitrosomonas causing reductions of from 68–93% of the control. These findings indicate that climax ponderosa pine communities minimize the conversion of ammonia-nitrogen to nitrate-nitrogen by chemically inhibiting nitrification.     

Chemistry, urease inhibition, and phytotoxic studies of binuclear vanadium(IV) complexes

Vanadium plays an important role in biological systems and exhibits a variety of bioactivities. In an effort to uncover the chemistry and biochemistry of vanadium with nitrogen- and oxygen-containing ligands, we report herein the synthesis and spectroscopic characterization of vanadium(IV) complexes with hydrazide ligands. Substituents on these ligands exhibit systematic variations of electronic and steric factors. Elemental and spectral data indicate the presence of a dimeric unit with two vanadium(IV) ions coordinated with two hydrazide ligands along with two H(2)O molecules. The stability studies of these complexes over time in coordinating solvent, DMSO, indicates binding of the solvent molecules to give [V2O2L2(H2O)2(DMSO)2]2+ (L=hydrazide ligand) and then conversion of it to a monomeric intermediate species, [VOL(DMSO)3]1+. Hydrazide ligands are inactive against urease, whereas vanadium(IV) complexes of these ligands show significant inhibitory potential against this enzyme and are found to be non-competitive inhibitors. These complexes also show low phytotoxicity indicating their usefulness for soil ureases. Structure-activity relationship studies indicate that the steric and/or electronic effects that may change the geometry of the complexes play an important role in their inhibitory potential and phytotoxicity.     

Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5

Binding of insulin to the insulin receptor initiates a cascade of protein phosphorylation and effector recruitment events leading to the activation of multiple distinct signaling pathways. Previous studies suggested that the diversity and specificity of insulin signal transduction are accomplished by both subcellular localization of receptor and the selective activation of downstream signaling molecules. The small GTPase Rab5 is a key regulator of endocytosis. Three Rab5 isoforms (Rab5a, -5b, and -5c) have been identified. Here we exploited the RNA interference technique to specifically knock down individual Rab5 isoforms to determine the cellular function of Rab5 in distinct insulin signaling pathways. Small interference RNA against a single Rab5 isoform had no effect on protein kinase B (PKB)/Akt or MAPK activation by insulin in NIH3T3 cells overexpressing human insulin receptor. However, simultaneous knockdown of all three Rab5 isoforms dramatically attenuated PKB/Akt activation by insulin without affecting MAPK activation. This inhibition of PKB/Akt activation was because of the impaired interaction between insulin receptor substrate 1 and the p85alpha subunit of phosphatidylinositol 3-kinase. These results indicate a requirement of Rab5 in presenting p85 to insulin receptor substrate 1. Additional evidence supporting a role for Rab5 was suggested by studies with GAPex-5, a vps9 domain containing exchange factor. Down-regulation of GAPex-5 impaired insulin-stimulated PKB/Akt activation. Collectively, this study indicates the involvement of Rab5 in insulin signaling.     

An Investigation into the Strength of the Association and Agreement Levels between Subjective and Objective Sleep Duration in Adolescents

Study Objectives

The majority of adolescent sleep research has utilized self-reported sleep duration and some have based information on a solitary question. Whilst some have claimed to have validated sleep survey data with objective actigraphy measures in adolescents, the statistical approach applied only demonstrates the strength of the association between subjective and objective sleep duration data and does not reflect if these different methods actually agree.

Methods

Data were collected as part of the Midlands Adolescents Schools Sleep Education Study (MASSES). Adolescents (n=225) aged 11-13 years provided estimates for weekday, weekend and combined sleep duration based on self-reported survey data, a 7-day sleep diary, and wrist-worn actigraphy.

Results

We assessed the strength of the relationship as well as agreement levels between subjective and objectively determined sleep duration (weekday, weekend and combined). Subjective diary sleep duration was significantly correlated with actigraphy estimates for weekday and weekend sleep duration r=0.30, p≤0.001 and r=0.31, p≤0.001 respectively. Pitman’s test demonstrated no significant difference in the variance between weekend sleep duration (r=0.09, p=0.16) and combined sleep duration (r=0.12, p=0.08) indicating acceptable agreement between actigraphy and sleep diary sleep duration only. Self-reported sleep duration estimates (weekday, weekend and combined) did not agree with actigraphy determined sleep duration.

Conclusions

Sleep diaries are a cost-effective alternative to survey/questionnaire data. Self-reported measures of sleep duration in adolescents do not agree with actigraphy measures and should be avoided where possible. Previous adolescent sleep studies that have utilized self-reported survey data may not provide a complete representation of sleep on the outcome measure of interest.     

Stress tolerance in transgenic tobacco seedlings that overexpress glutathione S-transferase/glutathione peroxidase

Overexpression of a tobacco glutathione S-transferase with glutathione peroxidase activity (GST/GPX) in transgenic tobacco (Nicotiana tabacum L.) enhanced seedling growth under a variety of stressful conditions. In addition to increased GST and GPX activity, transgenic GST/GPX-expressing (GST+) seedlings had elevated levels of monodehydroascorbate reductase activity. GST+ seedlings also contained higher levels of glutathione and ascorbate than wild-type seedlings and the glutathione pools were more oxidized. Thermal or salt-stress treatments that inhibited the growth of wild-type seedlings also caused increased levels of lipid peroxidation. These treatments had less effect on the growth of GST+ seedling growth and did not lead to increased lipid peroxidation. Stress-induced damage resulted in reduced metabolic activity in wild-type seedlings while GST+ seedlings maintained metabolic activity levels comparable to seedlings grown under control conditions. These results indicate that overexpression of GST/GPX in transgenic tobacco seedlings provides increased glutathione-dependent peroxide scavenging and alterations in glutathione and ascorbate metabolism that lead to reduced oxidative damage. We conclude that this protective effect is primarily responsible for the ability of GST+ seedlings to maintain growth under stressful conditions.     

Antibiotic discovery: combining isolation chip (iChip) technology and co-culture technique

Applied Microbiology and Biotechnology - Antibiotics had been a useful tool for treating bacterial infections since their discovery, but with the passage of time, the evolution of resistance among...     

Synthesis and anti-inflammatory activity of some selected aminothiophene analogs

Some 2-aminothiophene analogs 1-6 were synthesized and characterized. Among the tested compounds, compound 1 (IC50 121.47 microM) exhibited highest while the compound 5 showed least anti-inflammatory potential (IC50 422 microM).