51.
52.
Atilaw, Y., et al.
(författare)
Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata
2017
Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 22:2
Tidskriftsartikel (refereegranskat) abstract
In our search for new antiplasmodial agents, the CH2Cl2/CH3OH (1:1) extract of the roots of Tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3D7) strain of Plasmodium falciparum at a 10 mg/mL concentration. From this extract three new chalconoids, E-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (1, aequichalcone A), Z-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (2, aequichalcone B), 4-ethoxy-3-hydroxypraecansone B (3, aequichalcone C) and a new pterocarpene, 3,4:8,9-dimethylenedioxy-6a,11a-pterocarpene (4), along with seven known compounds were isolated. The purified compounds were characterized by NMR spectroscopic and mass spectrometric analyses. Compound 1 slowly converts into 2 in solution, and thus the latter may have been enriched, or formed, during the extraction and separation process. The isomeric compounds 1 and 2 were both observed in the crude extract. Some of the isolated constituents showed good to moderate antiplasmodial activity against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.
53.
Bains, Sandra, et al.
(författare)
Plastid Molecular Pharming II. Production of Biopharmaceuticals by Plastid Transformation
2017
Ingår i: Mini-Reviews in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1389-5575. ; 17:13, s. 1316-1330
Tidskriftsartikel (refereegranskat) abstract
Background: Higher plants have been used in medicine throughout human history. Method: While traditional medicinal uses relied on compounds produced naturally by plants, recent advances have enabled the use of plant-based factories to produce diverse agents including pharmaceuticals, antibiotics, and vaccines. The genes responsible for the production of these substances can be either transiently expressed in plants or integrated into their nuclear genome or plastid genome (plastome) by genetic transformation. This review focuses on the application of plastid transformation of higher plants to produce biopharmaceuticals for human applications that are neither antibiotics nor vaccines. Plastid transformation has several advantages over nuclear transformation and represents a minimal risk of transgene contamination to the environment via pollen grains because plastid genes are in most species normally maternally inherited and thus absent from pollen. Other advantages of sitedirected plastid insertion via homologous recombination include strong gene expression due to the plastid genome's high copy number and resistance to silencing, and the ability to achieve multi-gene expression with a single insertion step. Results: Compared to bacterial systems, plant-based bioreactors offer lower production costs, lower risks of human pathogen contamination, and the possibility of exploiting post-translational modification. Conclusion: Consequently, sustainable plant systems based on different species, plastids, and tissues could become an important source of added value in pharmaceutical production.
54.
Barclay, Victoria K H, et al.
(författare)
Trace analysis of fluoxetine and its metabolite norfluoxetine. Part II : Enantioselective quantification and studies of matrix effects in raw and treated wastewater by solid phase extraction and liquid chromatography-tandem mass spectrometry
2012
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1227, s. 105-114
Tidskriftsartikel (refereegranskat) abstract
The isotope-labeled compounds fluoxetine-d5 and norfluoxetine-d5 were used to study matrix effects caused by co-eluting compounds originating from raw and treated wastewater samples, collected in Uppsala, Sweden. The matrix effects were investigated by the determination of matrix factors (MF) and by a post-column infusion method. The matrix factors were determined to be 38–47% and 71–86% for the enantiomers of norfluoxetine-d5 and fluoxetine-d5, respectively. The influence of matrix effects when quantifying the enantiomers of the active pharmaceutical ingredient and the metabolite in wastewater samples with LC–MS/MS is discussed and methods to overcome the problem are presented. The enantiomeric concentrations of fluoxetine and its human metabolite norfluoxetine, quantified by a one-point calibration method, were 12–52 pM (3.5–16 ng L−1) in raw wastewater and 4–48 pM (1.2–15 ng L−1) in treated wastewater. Furthermore, the calculated enantiomeric fractions (EF) of the substances were found to be between 0.68 and 0.71 in both matrices. Neither the EF values for fluoxetine nor those for norfluoxetine were significantly different in the raw wastewater compared to the treated wastewater. Interestingly, the concentration of (S)-fluoxetine was found to be higher than the concentration of (R)-fluoxetine in both raw and treated wastewater. These results are different from other results presented in the literature, which shows that the relative concentrations of the enantiomers of a chiral active pharmaceutical ingredient might be significantly different in wastewater samples from different treatment systems. We report, for the first time, the concentrations of the enantiomers of norfluoxetine in wastewater samples. The concentrations of (S)-norfluoxetine were found to be higher than the concentration of (R)-norfluoxetine in the raw as well as in the treated wastewater samples.
55.
Bergum, Sartaz, et al.
(författare)
Bioactivities of extracts, debromolaurinterol and fucosterol from macroalgae species
2018
Ingår i: Tanzania Journal of Science. - Dar es Salaam. - 0856-1761 .- 2507-7961. ; 44:2, s. 104-116
Tidskriftsartikel (refereegranskat) abstract
Parasitic diseases including malaria, and other numerous microbial infections and physiological diseases are threatening the global population. Tanzanian coast shores are endowed with a variety of macroalgae (seaweeds), hitherto unsystematically explored to establish their biomedical potentials. Thus, antiplasmodial activity using malarial imaging assay, antimicrobial activity using microplate dilution technique, antioxidant activity using DPPH radical scavenging method and cytotoxicity using brine shrimp test were carried out on crude extracts from the selected species of algae (Acanthophora spicifera, Cystoseira myrica, Cystoseira trinodis, Laurencia filiformis, Padina boryana, Sargassum oligocystum, Turbinaria crateriformis, Ulva fasciata and Ulva reticulata) occurring along the coast of Tanzania. The extracts showed antimicrobial activities with MIC ranging from 0.3- 5.0 µg/mL against Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Cryptococcus neoformans; DPPH radical scavenging activity at EC50 1.0- 100 µg/mL and cytotoxicity on brine shrimp larvae with LC50 value ranging from20 - 1000 µg/mL. The extracts from C. myrica and P. boryana inhibited growth of Plasmodium falciparum (3D7 strain) by 80 and 71%, respectively at 40 µg/mL while a sesquiterpene debromolaurinterol (1) which was chromatographically isolated from C. myrica exhibited antiplasmodial activity with IC50 20 µM whereas a sterol fucosterol (2) from P. boryana showed weak activity at 40 µM. Bioactivities portrayed by the investigated extracts indicate their ingredients as potential sources of bioactive agents that warrant further explorations.
56.
Bhakat, Soumendranath, et al.
(författare)
Reaching beyond HIV/HCV: nelfinavir as a potential starting point for broad-spectrum protease inhibitors against dengue and chikungunya virus
2015
Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 5:104, s. 85938-85949
Tidskriftsartikel (refereegranskat) abstract
Drug repurposing or re-profiling has become an effective strategy to identify novel indications for already-approved drugs. In this study, peptidomimetic FDA-approved HIV/HCV inhibitors were explored for their potential to be repurposed for the inhibition of the replication of dengue (DENV) and chikungunya virus (CHIKV) by targeting the NS2B-NS3 and NSP2 protease, respectively. MM/GBSA-based binding free energy results put nelfinavir forward as a potential inhibitor of both dengue and chikungunya virus, which subsequently was further explored in a virus-cell-based assay for both viruses. Nelfinavir showed modest antiviral activity against CHIKV (EC50 = 14 +/- 1 mu M and a selectivity index of 1.6) and was slightly more active against DENV-2 (EC50 = 3.5 +/- 0.4 mu M and a selectivity index of 4.6). Even though the antiviral potency was limited, the fact that some activity was observed in these assays made it worthwhile exploring the potential and properties of nelfinavir as a stepping-stone compound: a more detailed computational analysis was performed to understand the binding mode, interaction, hydrogen bond distance, occupancy and minimum pharmacophoric features. The comprehensive data set that resulted from these analyses may prove to be useful for the development of novel DENV and CHIKV protease inhibitors.
57.
58.
Davidsson, Johan, 1967, et al.
(författare)
A Sagittal Plane Rotational Injury Rodent Model for Research on Traumatic Brain Injuries
2019
Ingår i: Neuromethods. - New York, NY : Springer New York. - 1940-6045 .- 0893-2336. ; 149, s. 61-75
Bokkapitel (övrigt vetenskapligt/konstnärligt) abstract
The model presented here produce brain injuries following sagittal plane rearward rotational acceleration in rats. During trauma, a rotating bar, which is tightly secured to the animal head, is impacted by a striker that causes the rotating bar and the animal head to rotate rearward; the acceleration phase is followed by a rotation at constant speed and gentle deceleration when the rotating bar contacts a padded stop. The total head angle change range from 25° to 30°. By adjusting the air pressure in the air-driven accelerator used to accelerate the striker, a large range of rotational accelerations can be achieved. This model can, depending on the striker velocity, produce subdural bleedings, graded widespread axonal injuries in the corpus callosum, the border between the corpus callosum, cortex, cerebellum, olfactory bulbs, and in some of the tracts in the brain stem. The model has been shown to produce degenerating axons. For lower rotational accelerations no apparent axonal injuries can be observed. The model produces only limited signs of contusion injury, and macrophage invasions, glial fibrillary acidic protein redistribution or hypertrophy, and blood–brain barrier changes are unusual. The model produces distinct S100 and Neurofilament Light serum concentration changes, thus indicating that blood vessel and glia cell injuries may occur. The rotational acceleration trauma model presented can produce graded axonal injury, is repeatable, and produce limited other types of TBIs and as such is useful in the study of injury biomechanics, diagnostics, and treatment strategies following diffuse axonal injury and most likely also following concussion.
59.
Delsing, Louise, et al.
(författare)
Enhanced xeno-free differentiation of hiPSC-derived astroglia applied in a blood-brain barrier model
2019
Ingår i: Fluids and Barriers of the Cns. - : Springer Science and Business Media LLC. - 2045-8118. ; 16:1
Tidskriftsartikel (refereegranskat) abstract
Background Human induced pluripotent stem cells (hiPSC) hold great promise for use in cell therapy applications and for improved in vitro models of human disease. So far, most hiPSC differentiation protocols to astroglia use undefined, animal-containing culture matrices. Laminins, which play an essential role in the regulation of cell behavior, offer a source of defined, animal-free culture matrix. Methods In order to understand how laminins affect astroglia differentiation, recombinant human laminin-521 (LN521), was compared to a murine Engelbreth-Holm-Swarm sarcoma derived laminin (L2020). Astroglia expression of protein and mRNA together with glutamate uptake and protein secretion function, were evaluated. Finally, these astroglia were evaluated in a coculture model of the blood-brain barrier (BBB). Results Astroglia of good quality were generated from hiPSC on both LN521 and L2020. However, astroglia differentiated on human LN521 showed higher expression of several astroglia specific mRNAs and proteins such as GFAP, S100B, Angiopoietin-1, and EAAT1, compared to astroglia differentiated on murine L2020. In addition, glutamate uptake and ability to induce expression of junction proteins in endothelial cells were affected by the culture matrix for differentiation. Conclusion Our results suggest that astroglia differentiated on LN521 display an improved phenotype and are suitable for coculture in a hiPSC-derived BBB model. This provides a starting point for a more defined and robust derivation of astroglia for use in BBB coculture models.
60.
El-Seedi, Hesham R., et al.
(författare)
Recent insights into the biosynthesis and biological activities of natural xanthones
2010
Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 17:9, s. 854-901
Forskningsöversikt (refereegranskat) abstract
This review focuses on recent advances in our understanding of the complex biosynthetic pathways and diverse biological activities of naturally occurring xanthones. The biosynthesis section covers studies published from 1989 to 2008 on xanthone production in plants and fungi, while the bioactivity review presents tabulated activities of more than 250 xanthones described in studies published from 2001 to 2008, together with structural information and indications of their wide-ranging potential uses as pharmacological tools. A large number of relevant papers have been published on these subjects (128 cited here), illustrating the diversity of the xanthones and their possible uses.
