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| 2. |
- Dasari, Bhanudas, et al.
(författare)
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Macrocyclic Glycohybrid Toolbox Identifies Novel Antiangiogenesis Agents from Zebrafish Assay
- 2013
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Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 15:3, s. 432-435
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A practical and modular approach to obtain a diverse set of 14-membered macrocyclic compounds from carbohydrates is developed that utilizes functional groups at C-1 and C-5. The evaluation of this toolbox in various zebrafish assays led to the identification of 2.7f as an antianglogenesis agent.
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| 3. |
- Guduru, Shiva Krishna Reddy, et al.
(författare)
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Tetrahydroquinoline-Derived Macrocyclic Toolbox : The Discovery of Antiangiogenesis Agents in Zebrafish Assay
- 2013
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 4:7, s. 666-670
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Tidskriftsartikel (refereegranskat)abstract
- A novel approach to incorporate the macrocyclic rings onto the privileged substructure, i.e. tetrahydroquinoline scaffold, is developed. The presence of an amino acid-derived moiety in the macrocyclic skeleton provides an opportunity to modulate the nature of the chiral side chain. Further, evaluation in a zebrafish screen identified three active small molecules (2.5b, 3.2d, and 4.2) as antiangiogenesis agents at 2.5 mu M.
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| 4. |
- Jogula, Srinivas, et al.
(författare)
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Building a Macrocyclic Toolbox from C-Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay
- 2013
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 2013:23, s. 5036-5040
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Tidskriftsartikel (refereegranskat)abstract
- We report the synthesis of four different types of macrocyclic-derived glycohybrids from carbohydrates that have an amino acid moiety in the large-ring skeleton. These macrocyclic glycohybrids were obtained from -C-1H- and -C-1H-linked carbohydrates. In one series, we utilized ring-closing metathesis as the stitching technology to obtain two different macrocycles, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The click approach was the key reaction in our second series to obtain two other macrocyclic compounds, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Interestingly, in both cases, the macrocyclic compounds that have a cis relationship (i.e., axial-axial orientation) between C-1H and C-5H showed activity and their other diastereomers (i.e., equatorial-axial C-1H and C-5 H) with a trans relationship did not show any effect.
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| 5. |
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| 6. |
- Aeluri, Madhu, et al.
(författare)
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An Intramolecular Heck Approach To Obtain 17-Membered Macrocyclic Diversity and the Identification of an Antiangiogenesis Agent from a Zebrafish Assay
- 2013
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; :19, s. 3955-3958
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Tidskriftsartikel (refereegranskat)abstract
- We report a practical and modular approach to obtain two different types of 17-membered ring macrocyclic compounds through an intramolecular Heck reaction. These macrocyclic compounds are functionalized, that is, they contain two contiguous stereogenic hydroxy functional groups and an amino acid moiety in the macrocyclic ring skeleton. The macrocycles were then screened against a zebrafish assay to determine the antiangiogenesis activity of these small molecules. Macrocyclic compound 2.2a was identified as a potent inhibitor at 2.5 M, whereas its acyclic precursor and the other related macrocyclic compounds did not show any effect.
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| 7. |
- Archer, Amena, et al.
(författare)
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The Liver X-Receptor (Lxr) Governs Lipid Homeostasis in Zebrafish during Development
- 2012
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Ingår i: Open journal of endocrine and metabolic diseases. - : Scientific Research Publishing. - 2165-7424 .- 2165-7432. ; 2:4, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- The liver-X-receptors (LXRs) act as cholesterol sensors and participate in the regulation of lipid and cholesterol metabolism. The objective of this study was to determine the role of LXR during development using the zebrafish model. By in situ hybridization we showed distinct expression of lxr in the brain and the retina in the developing and adult zebrafish. Lxr ligand activation affected the expression of genes involved in lipid metabolism in zebrafish adult brain and eye as well as in zebrafish embryos. Morpholino knock down of lxr resulted in an overall impaired lipid deposition as determined by oil red O staining particularly in the head and around the eyes, and to significantly elevated levels of both total and free cholesterol in the yolk of lxr morphant embryos. The expression of genes involved in lipid and cholesterol metabolism was also changed in the lxr morphants. Furthermore, alcian blue staining revealed malformation of the pharyngeal skeleton in the lxr morphant. Our data show that Lxr is an important component of the regulatory network governing the lipid homeostasis during zebrafish development, which in turn may support a role of Lxr for normal development of the central nervous sytem, including the retina.
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| 8. |
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| 9. |
- Hallgren, Stefan, 1978-, et al.
(författare)
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Cloning, sequencing and In situ localisation of guppy brain aromatase, cyp19b
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Oestrogens are biosynthesised by cytochrome p450-aromatase (Cyp19). Brain oestrogens serve several important functions of which nerve protection, cell proliferation, nerve development and behaviour control are a few. Teleost brain aromatase activity is exceptionally high (between 100-1000 times) compared to mammals and birds. We have successfully cloned and sequenced a 950 bp long partial fragment of the guppy CYP19B gene (PrCyp19b) derived from adult brain mRNA. Sequence alignment of translated amino acid sequence shows PrCYP19b having high sequence similarity to teleost brain aromatase. Anatomical distribution of PrCYP19b expression in adult guppy brains was studied using in situ-hybridisation with an antisense riboprobe synthesised from the cloned PrCYP19b gene. Expression of brain aromatase appeared at ventricular surfaces of the ventral telencephalic zones and the pre-optic area, in the hypothalamus, the pituitary gland, optic tectum and the cerebellum. This pattern is similar to previously reported distribution of brain aromatase in other teleosts. Measurement of brain aromatase activity in telencephalon, mesencephalon/diencephalon and rhombencephalon revealed female guppies producing the most oestrogens in mesencephalon/diencephalon, whereas males produces the most oestrogens in both telencephalon and mesencephalon/diencephalon. This indicates that brain oestrogen production is sexually dimorphic in the guppy and may serve different functions in the two genders.
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| 10. |
- Hallgren, Stefan, et al.
(författare)
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Cloning, sequencing and In situ localisation of guppy brain aromatase, cyp19b
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Oestrogens are biosynthesised by cytochrome p450-aromatase (Cyp19). Brain oestrogens serve several important functions of which nerve protection, cell proliferation, nerve development and behaviour control are a few. Teleost brain aromatase activity is exceptionally high (between 100-1000 times) compared to mammals and birds. We have successfully cloned and sequenced a 950 bp long partial fragment of the guppy CYP19B gene (PrCyp19b) derived from adult brain mRNA. Sequence alignment of translated amino acid sequence shows PrCYP19b having high sequence similarity to teleost brain aromatase. Anatomical distribution of PrCYP19b expression in adult guppy brains was studied using in situ-hybridisation with an antisense riboprobe synthesised from the cloned PrCYP19b gene. Expression of brain aromatase appeared at ventricular surfaces of the ventral telencephalic zones and the pre-optic area, in the hypothalamus, the pituitary gland, optic tectum and the cerebellum. This pattern is similar to previously reported distribution of brain aromatase in other teleosts. Measurement of brain aromatase activity in telencephalon, mesencephalon/diencephalon and rhombencephalon revealed female guppies producing the most oestrogens in mesencephalon/diencephalon, whereas males produces the most oestrogens in both telencephalon and mesencephalon/diencephalon. This indicates that brain oestrogen production is sexually dimorphic in the guppy and may serve different functions in the two genders.
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