Quinazolinone fungal efflux pump inhibitors. Part 2: In vitro structure-activity relationships of (N-methyl-piperazinyl)-containing derivatives

Structure-activity relationships of a novel series of fungal efflux pump inhibitors with respect to potentiation of the activity of fluconazole against strains of Candida albicans and Candida glabrata over-expressing ABC-type efflux pumps are systematically explored.     

New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids

During this study, one new coumarin; 7-O-beta-D-glucopyranoside-2H-1-benzopyran-2-one (1) and three quinoline alkaloids; 3-hydroxy, 2, 2, 6-trimethyl-3, 4, 5, 6-tetrahydro-2H-pyrano[3,2-c] quinoline 5-one (2), ribalinine (3) and methyl isoplatydesmine (4) were isolated from the aerial parts of Skimmia laureola and their structures established by spectroscopic studies. Compounds 2-4 were found to be linear mixed type inhibitors of acetylcholinesterase (K(i) = 110.0, 30.0 and 30.0 microM, respectively). Compounds 2 and 3 were also found to be linear mixed type inhibitors of butyrylcholinesterase, while compound 4 was a noncompetitive inhibitor of the enzyme (K(i) = 90.0, 70.0 and 19.0 microM, respectively). The inhibition of acetyl- and butyryl-cholinesterase enzymes persists as the most promising therapeutic strategy for activating the impaired cholinergic functions in Alzheimer's disease and related dementias. Compound 4 also showed dose-dependent spasmolytic activity in the isolated rabbit jejunum intestinal preparation by relaxing the spontaneous (EC50 = 0.1 mg/mL) and K(+)-induced contractions (EC50 = 0.4 mg/mL), suggesting that the spasmolytic effect of compound 4 is mediated through the blockade of voltage-dependent Ca2+ channels.     

Phosphatase Activity Toward Abnormally Phosphorylated τ: Decrease in Alzheimer Disease Brain

Abstract: Microtubule-associated protein τ is abnormally hyperphosphorylated and aggregated in affected neurons of Alzheimer disease brain. This hyperphosphorylated τ can be dephosphorylated at some of the abnormal phosphorylated sites by purified protein phosphatase-1, 2A, and 2B in vitro. In the present study, we have developed an assay to measure protein phosphatase activity toward τ-1 sites (Ser¹⁹⁹/Ser²⁰²) using the hyperphosphorylated τ isolated from Alzheimer disease brain as substrate. Using this assay, we have identified that in normal brain, protein phosphatase-2A and 2B and, to a lesser extent, 1 are involved in the dephosphorylation of τ. The K _m values of dephosphorylation of the hyperphosphorylated τ by protein phosphatase-2A and 2B are similar. The τ phosphatase activity is decreased by ∼30% in brain of Alzheimer disease patients compared with those of age-matched controls. These findings suggest that a defect of protein phosphatase could be the cause of the abnormal hyperphosphorylation of τ in Alzheimer disease.     

Galinsosides A and B,bioactive flavanone glucosides from Galinsoga parviflora

Galinsosides A (1) and B (2), new flavanone glucosides together with two known flavanones, 7,3′,4′-trihydroxyflavanone (3) and 3,5,7,3′,4′-pentahydroxyflavanone (4) have been isolated from an ethyl acetate- soluble fraction of Galinsoga parviflora. Their structures were assigned on the basis of spectral studies. Compound 1 showed significant antioxidant and urease inhibitory activity while compound 2 was moderately active. On the other hand, 2 showed inhibitory potential against α-glucosidase.     

Foliar characteristics,cambial activity and wood formation in Azadirachta indica A. Juss. as affected by coal–smoke pollution

This study, aimed at elucidating changes in the foliar and cambial behavior in Azadirachta indica (Neem tree) due to coal-smoke pollution, has revealed inhibitory effects of pollution stress on leaf pigments concentrations, nitrate reductase activity and the contents of reducing sugars and total N content, whereas stimulatory effects were given on stomatal index and nitrate and sulphur contents. Under smoke effects, stomatal conductance was low, leading to a drop in the net photosynthetic rate and a rise in the internal CO₂ concentration of leaf. Cambial reactivation in the stem was delayed at the polluted site. Although the total span of the cambial activity was reduced, greater amount of wood was observed to accumulate in the stem axis under heavy pollution stress. Vessel proportion in the wood increased, whereas size of vessel elements and xylem fibers decreased. “Vulnerability factor” (ratio between mean vessel diameter and mean vessel abundance) and “mesomorphic ratio” (multiplication product of vulnerability factor and mean length of vessel element) of the stem–wood, both declined with increase in the pollution stress, thus indicating a tendency of the species for shifting towards xeromorphy when grown under stress. Given the opposite trends of photosynthetic rate and wood increment, the carbon-partitioning pattern rather than the photosynthetic rate seems to have influenced the accumulation of new wood. The Neem tree proves to be suitable for growing in the polluted areas.     

Encapsulation of recombinant <Emphasis Type="Italic">E. coli</Emphasis> expressing cyclopentanone monooxygenase in polyelectrolyte complex capsules for Baeyer–Villiger biooxidation of 8-oxabicyclo[3.2.1]oct-6-en-3-one

Recombinant Escherichia coli cells, over-expressing cyclopentanone monooxygenase activity, were immobilized in polyelectrolyte complex capsules, made of sodium alginate, cellulose sulfate, poly(methylene-co-guanidine), CaCl₂ and NaCl. More than 90% of the cell viability was preserved during the encapsulation process. Moreover, the initial enzyme activity was fully maintained within encapsulated cells while it halved in free cells. Both encapsulated and free cells reached the end point of the Baeyer–Villiger biooxidation of 8-oxabicyclo[3.2.1]oct-6-en-3-one to 4,9-dioxabicyclo[4.2.1]non-7-en-3-one at the same time (48 h). Similarly, the enantiomeric excess above 94% was identical for encapsulated and free cells.     

Advances in Salt Tolerance of Some Major Fiber Crops Through Classical and Advanced Biotechnological Tools: A Review

Journal of Plant Growth Regulation - Plant biofibers are of great economic and commercial importance. Among various fiber producing crops, cotton (Gossypium hirsutum L.), hemp (Cannabis sativa L.),...     

Lead-induced oxidative stress and metabolic alterations in <Emphasis Type="Italic">Cassia angustifolia</Emphasis> Vahl.

Forty-five-days old plants of Indian senna (Cassia angustifolia Vahl.) were subjected to 0–500 μM lead acetate (Pb-Ac) in pot culture. Changes in contents of thiobarbituric acid reactive substances (TBARS), ascorbate, glutathione, proline, sennosides (a+b), and activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), and catalase (CAT) were studied at pre-flowering (60 d after sawing, DAS), flowering (90 DAS) and post-flowering (120 DAS) stages of plant development. Compared with the controls, the Pb-Ac treated plants showed an increase in contents of TBARS, dehydroascorbate, oxidized and total glutathione at all stages of growth. However, sennoside yield and contents of ascorbate and reduced form of glutathione declined. Proline content increased at 60 DAS but declined thereafter. Activities of SOD, APX, GR and CAT were markedly increased. Sennoside content was higher at 60 and 90 DAS but lower at 120 DAS, compared to the control.     

Linking larval nutrition to adult reproductive traits in the European corn borer Ostrinia nubilalis

Throughout an organism's lifetime, resources are strategically allocated to many different functions, including reproduction. Reproduction can be costly for both sexes; females produce nutrient‐rich eggs, whereas males of many species produce large and complex ejaculates. In capital breeding insects, nutrients are mainly acquired during the larval period, yet allocation decisions impact the reproductive fitness of adults. The present study examines the effect of larval dietary nitrogen on both male and female reproductive traits in the European corn borer moth Ostrinia nubilalis Hübner, whose adults do not feed and whose males transfer a large, nitrogen‐rich spermatophore. One day post‐eclosion, O. nubilalis adults reared on one of three different diets (3.0%, 1.6%, or 1.1% nitrogen) are mated and two experiments are undertaken: one to measure nitrogen and carbon content of male ejaculates, and the other to determine female fecundity and fertility. Although male larval diet does not alter the percentage nitrogen content of adult somatic tissue, males reared on the higher nitrogen diet (3.0%) produce spermatophores with increased nitrogen relative to somatic nitrogen. Furthermore, females raised on the 3.0% nitrogen diet receive spermatophores with lower carbon : nitrogen ratios and thus more nitrogen. Overall, females lay more eggs as their larval dietary nitrogen increases, although they lay fewer eggs when their mates are raised on the higher (3.0%) nitrogen diet. This suggests that O. nubilalis females may use male‐derived nitrogen not to supplement egg production, but rather for somatic maintenance. Overall, the present study furthers our understanding of how larval diet can affect adult fitness in Lepidoptera.