| 91. |
- Roman, Erika, et al.
(författare)
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Variations in opioid peptide levels during the estrous cycle in Sprague-Dawley rats
- 2006
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Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 40:3, s. 195-206
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Tidskriftsartikel (refereegranskat)abstract
- The estrous cycle, with its various hormonal conditions, may provide us with the means of understanding how endocrine states relate to opioid mechanisms. There has been increasing experimental support for interaction between sex steroids and opioid peptides in the central nervous system. Here, we describe fluctuations in endogenous brain immunoreactive (ir) peptide levels during various phases of the estrous cycle in the female Sprague-Dawley rat. Ir levels of dynorphin A, dynorphin B, Leu-enkephalin-Arg(6), Met-enkephalin-Arg(6)Phe(7) and nociceptin/orphanin FQ were measured in the pituitary gland and in 10 areas of the brain during the diestrus, proestrus and estrus phase. In several areas of the brain, basal levels of endogenous opioid peptides showed variation during the course of the estrous cycle. Significant differences were found between the diestrus state and the proestrus and/or estrus conditions, particularly in the nucleus accumbens, caudate putamen and the substantia nigra. The ir levels of the endogenous peptide nociceptin/orphanin FQ became altered in only one of the areas measured, indicating less variance during the estrous cycle. Correlation analyses revealed that significant associations between dynorphin A or dynorphin B and Leu-enkephalin-Arg(6) were found more often during estrus than during the diestrus and proestrus conditions. The ratio between the ir levels of Leu-enkephalin-Arg(6), a cleavage product of the enzymatic conversion of dynorphin peptides into shorter peptides in vivo, and dynorphin peptides was calculated. The significantly lower ratio between Leu-enkephalin-Arg(6) and dynorphin B in diestrus than in proestrus and estrus also indicates cyclic fluctuations in the enzymatic cleavage of dynorphin. These findings are discussed in relation to the possible role of interactions between sex steroids and opioid peptide mechanisms during the normal estrous cycle.
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| 92. |
- Zelleroth, Sofia, 1990-, et al.
(författare)
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Structurally different anabolic androgenic steroids reduce neurite outgrowth and neuronal viability in primary rat cortical cell cultures
- 2021
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 210
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Tidskriftsartikel (refereegranskat)abstract
- The illicit use of anabolic androgenic steroids (AAS) among adolescents and young adults is a major concern due to the unknown and unpredictable impact of AAS on the developing brain and the consequences of this on mental health, cognitive function and behaviour. The present study aimed to investigate the effects of supra-physiological doses of four structurally different AAS (testosterone, nandrolone, stanozolol and trenbolone) on neurite development and cell viability using an in vitro model of immature primary rat cortical cell cultures. A high-throughput screening image-based approach, measuring the neurite length and number of neurons, was used for the analysis of neurite outgrowth. In addition, cell viability and expression of the Tubb3 gene (encoding the protein beta-III tubulin) were investigated. Testosterone, nandrolone, and trenbolone elicited adverse effects on neurite outgrowth as deduced from an observed reduced neurite length per neuron. Trenbolone was the only AAS that reduced the cell viability as indicated by a decreased number of neurons and declined mitochondrial function. Moreover, trenbolone downregulated the Tubb3 mRNA expression. The adverse impact on neurite development was neither inhibited nor supressed by the selective androgen receptor (AR) antagonist, flutamide, suggesting that the observed effects result from another mechanism or mechanisms of action that are operating apart from AR activation. The results demonstrate a possible AAS-induced detrimental effect on neuronal development and regenerative functions. An impact on these events, that are essential mechanisms for maintaining normal brain function, could possibly contribute to behavioural alterations seen in AAS users.
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| 93. |
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| 94. |
- Abdissa, Negera, et al.
(författare)
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Cytotoxic Quinones from the roots of Aloe dawei
- 2014
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Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 19:3, s. 3264-3273
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Tidskriftsartikel (refereegranskat)abstract
- Seven naphthoquinones and nine anthraquinones were isolated from the roots of Aloe dawei by chromatographic separation. The purified metabolites were identified by NMR and MS analyses. Out of the sixteen quinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone is a new compound. Two of the isolates, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione and 1-hydroxy-8-methoxy-3-methylanthraquinone showed high cytotoxic activity (IC50 1.15 and 4.85 µM) on MCF-7 breast cancer cells, whereas the others showed moderate to low cytotoxic activity against MDA-MB-231 (ER Negative) and MCF-7 (ER Positive) cancer cells.
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| 95. |
- Abu-Youssef, Morsy A.M., et al.
(författare)
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Synthesis and Structure of Silver Complexes with Nicotinate-Type Ligands Having Antibacterial Activities against Clinically Isolated Antibiotic Resistant Pathogens
- 2007
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 46:15, s. 5893-5903
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and low-temperature X-ray crystal structures of five new silver complexes, [Ag2-μ-O,O'(2-aminonicotinium)2(NO3)2]n (7), [Ag(isonicotinamide)2-μ-O,O'(NO3)]2 (8), [Ag(ethyl nicotinate)2](NO3) (9), [Ag(ethyl isonicotinate)2(NO3)] (10), and [Ag(methyl isonicotinate)2(H2O)](NO3) (11), are presented and fully characterized by spectral and elemental analysis. The antimicrobial activities of these complexes were screened using 12 different clinical isolates belonging to four pathogenic bacteria, S. aureus, S. pyogenes, P. mirabilis, and Ps. Aeruginosa, all obtained from diabetic foot ulcers. These tested bacteria were resistant for at least 10 antibiotics commonly used for treatment of diabetic foot ulcers. Compounds 7 and 8 had considerable activity against Ps. Aeruginosa (MIC values 2-8 µg/mL), compound 9 against S. aureus (MIC 4-16 µg/mL) and S. pyogenes (MIC 2-4 µg/mL), and also 9 and 11 against P. mirabilis (MIC 1-16 µg/mL). All complexes were non-toxic for daphnia at concentrations above 512 µg/mL overnight.
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| 96. |
- Adeyemi, Ahmed, 1986-
(författare)
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Palladium(0)-Catalyzed Synthesis of Spirocycles and Supercritical Chemistry using a Resistively Heated Flow Reactor
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This doctoral thesis focusses on an effective and selective approach to the synthesis of spirocycles using palladium(0)-catalyzed Mizoroki-Heck reactions. In addition, selective and efficient chemistry was highlighted by the design and evaluation of a novel resistively heated system for continuous flow (CF) synthesis for high-temperature and high-pressure applications.Paper I described the design and evaluation of a novel resistively heated CF system. The design of a low-cost, simple, robust, and effective CF system involving a resistively heated steel reactor capable of delivering 400 °C and 200 bar was reported. The reactor was evaluated with esterification, transesterification and direct carboxylic acid to nitrile conversions using supercritical ethanol, methanol and acetonitrile respectively. Diels-Alder reactions under neat conditions were also carried out at high temperature and pressure.Paper II reported the synthesis of spirooxindoles by a selective application of the palladium(0)-catalyzed Mizoroki-Heck spirocyclization. The precursors for the reaction were synthesized by coupling 2-iodoanilines with esters derived from enantiomerically pure (+)-Vince lactam decorated with the bulky, directing 2,5-dimethylpyrrole protecting group. Ten different spirooxindoles were reported with good yields and high regio- and stereoselectivity. Functionalization of a synthesized spirooxindole was done by a palladium(0)-catalyzed alkoxycarbonylation, followed by selective deprotections.In Paper III, ether precursors were synthesized from (+)-Vince lactam, via a Mitsunobu reaction with the corresponding iodophenols. The precursors were later subjected to conditions for intramolecular Mizoroki-Heck reaction. Overall, 12 spiroethers were synthesized in useable yields, regioselectivity up to 98% and with excellent diastereoselectivity (d.e.>98%). Further functionalization to mono-protected rigidified amino acids was also demonstrated.
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| 97. |
- Alhalaweh, Amjad, et al.
(författare)
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Physical stability of drugs after storage above and below the glass transition temperature : Relationship to glass-forming ability
- 2015
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 495:1, s. 312-317
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Tidskriftsartikel (refereegranskat)abstract
- Amorphous materials are inherently unstable and tend to crystallize upon storage. In this study, we investigated the extent to which the physical stability and inherent crystallization tendency of drugs are related to their glass-forming ability (GFA), the glass transition temperature (T-g) and thermodynamic factors. Differential scanning calorimetry was used to produce the amorphous state of 52 drugs [ 18 compounds crystallized upon heating (Class II) and 34 remained in the amorphous state (Class III)] and to perform in situ storage for the amorphous material for 12 h at temperatures 20 degrees C above or below the T-g. A computational model based on the support vector machine (SVM) algorithm was developed to predict the structure-property relationships. All drugs maintained their Class when stored at 20 degrees C below the T-g. Fourteen of the Class II compounds crystallized when stored above the T-g whereas all except one of the Class III compounds remained amorphous. These results were only related to the glass-forming ability and no relationship to e. g. thermodynamic factors was found. The experimental data were used for computational modeling and a classification model was developed that correctly predicted the physical stability above the T-g. The use of a large dataset revealed that molecular features related to aromaticity and pi-pi interactions reduce the inherent physical stability of amorphous drugs.
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| 98. |
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| 99. |
- Asimus, Sara, 1976, et al.
(författare)
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Artemisinin--a possible CYP2B6 probe substrate?
- 2009
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Ingår i: Biopharmaceutics & drug disposition. - : Wiley. - 1099-081X .- 0142-2782. ; 30:5, s. 265-75
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To compare in vitro metabolism rates for artemisinin and the CYP2B6 substrates, bupropion, propofol and efavirenz in human liver microsomes. METHODS: Rate constants of artemisinin, bupropion, propofol and efavirenz metabolism by human liver microsomes from a panel of 12 donors, with different levels of CYP2B6 activity, were estimated in WinNonlin. Correlations between the metabolic rate constant for artemisinin and the other CYP2B6 substrates were examined. RESULTS: Artemisinin and propofol depletion data in human liver microsomes were described by first order kinetic models. For bupropion and efavirenz, metabolite formation data were incorporated in the model. Rate constants varied considerably for all substrates. There was a high degree of correlation of rate constants between substrates (r> or =0.87, p<0.001). CONCLUSIONS: The rate of in vitro metabolism of artemisinin was correlated significantly to that of bupropion, propofol and efavirenz, suggesting artemisinin to be a potential alternative marker to assess CYP2B6 activity. Further studies characterizing the metabolic fate of artemisinin are needed in order to evaluate its utility as an in vitro and in vivo CYP2B6 probe substrate, since CYP2B6 might not be the only CYP isoform involved in the depletion of artemisinin.
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| 100. |
- Atilaw, Y., et al.
(författare)
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Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata
- 2017
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Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 22:2
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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.
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