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Frankfurt am Main, Germany

Egecioglu E.,Gothenburg University | Jerlhag E.,Gothenburg University | Salome N.,Gothenburg University | Skibicka K.P.,Gothenburg University | And 7 more authors.
Addiction Biology | Year: 2010

We investigated whether ghrelin action at the level of the ventral tegmental area (VTA), a key node in the mesolimbic reward system, is important for the rewarding and motivational aspects of the consumption of rewarding/palatable food. Mice with a disrupted gene encoding the ghrelin receptor (GHS-R1A) and rats treated peripherally with a GHS-R1A antagonist both show suppressed intake of rewarding food in a free choice (chow/rewarding food) paradigm. Moreover, accumbal dopamine release induced by rewarding food was absent in GHS-R1A knockout mice. Acute bilateral intra-VTA administration of ghrelin increased 1-hour consumption of rewarding food but not standard chow. In comparison with sham rats, VTA-lesioned rats had normal intracerebroventricular ghrelin-induced chow intake, although both intake of and time spent exploring rewarding food was decreased. Finally, the ability of rewarding food to condition a place preference was suppressed by the GHS-R1A antagonist in rats. Our data support the hypothesis that central ghrelin signaling at the level of the VTA is important for the incentive value of rewarding food. © 2010 Society for the Study of Addiction. Source


Leepasert T.,University of Vienna | Leepasert T.,Kasetsart University | Shahabi M.,University of Vienna | Shanab K.,University of Vienna | And 6 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2013

A new series of substituted tri-/tetraazabenzo[3,2-a]fluorene-5,6-diones and their corresponding oxime derivatives have been synthesized and spectroscopically characterized. The antiproliferative activities of all compounds were evaluated on at least three different cell lines. © 2013 Elsevier Ltd. All rights reserved. Source


Prinz H.,University of Munster | Schmidt P.,AeternaZentaris GmbH | Bohm K.J.,Leibniz Institute for Age Research | Baasner S.,AeternaZentaris GmbH | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2011

A novel series of phenylimino-10H-anthracen-9-ones and 9-(phenylhydrazone)- 9,10-anthracenediones were synthesized and evaluated for interaction with tubulin and for cytotoxicity against a panel of human tumor cell lines. The 10-(3-hydroxy-4-methoxy-phenylimino)-10H-anthracen-9-one 15h and its dichloro analog 16b were identified as potent inhibitors of tumor cell growth (16b, IC 50 K562 0.11 μM), including multidrug resistant phenotypes. Compound 15h had excellent activity as an inhibitor of tubulin polymerization. Concentration-dependent cell cycle analyzes by flow cytometry confirmed that KB/HeLa cells treated by 15h and 16b were arrested in the G2/M phases of the cell cycle. In competition experiments, 15h strongly displaced radiolabeled colchicine from its binding site on tubulin, showing IC 50 values similar to that of colchicine. The results obtained demonstrate that the antiproliferative activity is related to the inhibition of tubulin polymerization. © 2011 Elsevier Ltd. All rights reserved. Source


Nickel H.C.,University of Munster | Schmidt P.,AeternaZentaris GmbH | Bohm K.J.,Leibniz Institute for Age Researche Fritz Lipmann Institute FLI | Baasner S.,AeternaZentaris GmbH | And 5 more authors.
European Journal of Medicinal Chemistry | Year: 2010

A novel series of 1,5-and 1,8-disubstituted 10-benzylidene-10H-anthracen-9- ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones was synthesized to assess the substituent effects on biological activity. The 3-hydroxy-2,4- dimethoxy-benzylidene analogue 16h displayed strong antiproliferative activity against several tumor cell lines,including multi-drug resistant phenotypes. Flow cytometric studies showed that KB/HeLa cells treated by elected compounds were arrested in the G2/M phases of the cell cycle. Among the compounds tested for inhibition of tubulin polymerization,14 compounds proved to be exceptionally active with IC50 values < 1 mM. In the 1,5-dichloro-derived series of benzy-lideneanthracenones,E/Z isomers were separated and biological effects were monitored. We found that the olefinic geometry had no significant effect on biological activity. Furthermore,the E isomeric 1,5-dichloro-substituted phenacylidenes entirely proved to be more potent inhibitors of tubulin polymerization than the recently described 10-(2-oxo-2-phenylethylidene)-10H- anthracen-9-ones. In conclusion,the present study improves understanding of the action of anthracenone-based tubulin polymerization inhibitors and contributes to the design of further potent anti-tubulin drugs. © 2010 Elsevier Masson SAS. All rights reserved. Source


Shanab K.,University of Vienna | Schirmer E.,University of Vienna | Knafl H.,University of Vienna | Wulz E.,University of Vienna | And 6 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2010

A series of azanaphthoquinone pyrrolo-annelated derivatives attached to basic side chains have been synthesized. The antiproliferative activities of all compounds were evaluated on at least four different cell lines. The effects on cell cycle and intercalation were investigated. © 2010 Elsevier Ltd. All rights reserved. Source

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