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Moczar I.,Hungarian Academy of Sciences | Huszthy P.,Hungarian Academy of Sciences | Huszthy P.,Budapest University of Technology and Economics | Mezei A.,Budapest University of Technology and Economics | And 5 more authors.
Tetrahedron | Year: 2010

Four new achiral and four new chiral monoazacrown ethers containing an acridinone or an N-methylacridinone fluorescent signalling unit were prepared by reacting chloromethyl-substituted acridinone derivatives with achiral monoazacrown ethers with different cavity sizes and enantiopure monoaza-18-crown-6 ethers having two methyl and two isobutyl groups on their chiral centres, respectively. The operation of these chemosensors is based on the photoinduced electron transfer (PET) process, thus they show fluorescence enhancement in the presence of cationic guests. Their fluorescent behaviour as well as their complexation properties towards selected metal ions and the enantiomers of α-(1-naphthyl)ethylammonium perchlorate and potassium mandelate were examined. © 2009 Elsevier Ltd. All rights reserved.

Gulyas B.,Karolinska Institutet | Pavlova E.,Karolinska Institutet | Kasa P.,University of Szeged | Gulya K.,University of Szeged | And 8 more authors.
Neurochemistry International | Year: 2011

In the human brain the monoaminooxidase-B enzyme or MAO-B is highly abundant in astrocytes. As astrocyte activity and, consequently, the activity of the MAO-B enzyme, is up-regulated in neuroinflammatory processes, radiolabelled analogues of deprenyl may serve as an imaging biomarker in neuroinflammation and neurodegeneration, including Alzheimer's disease. In the present study [11C]-l-deprenyl, the PET radioligand version of l-deprenyl or selegiline®, a selective irreversible MAO-B inhibitor was used in whole hemisphere autoradiographic experiments in human brain sections in order to test the radioligand's binding to the MAO-B enzyme in human brain tissue, with an eye on exploring the radioligand's applicability as a molecular imaging biomarker in human PET studies, with special regard to diagnostic detection of reactive astrogliosis. Whole hemisphere brain sections obtained from Alzheimer patients and from age matched control subjects were examined. In control brains the binding of [11C]-l-deprenyl was the highest in the hippocampus, in the basal ganglia, the thalamus, the substantia nigra, the corpus geniculatum laterale, the nucleus accumbens and the periventricular grey matter. In Alzheimer brains significantly higher binding was observed in the temporal lobes and the white matter. Furthermore, in the Alzheimer brains in the hippocampus, temporal lobe and white matter the binding negatively correlated with Braak stages. The highest binding was observed in Braak I-II, whereas it decreased with increasing Braak grades. The increased regional binding in Alzheimer brains coincided with the presence of an increased number of activated astrocytes, as demonstrated by correlative immunohistochemical studies with GFAP in adjacent brain slices. Deprenyl itself as well as the MAO-B antagonist rasagiline did effectively block the binding of the radioligand, whereas the MAO-A antagonist pirlindole did not affect it. Compounds with high affinity for the PBR system did not block the radioligand binding either, providing evidence for the specificity of [11C]-l-deprenyl for the MAO-B enzyme. In conclusion, the present observations indicate that [11C]-l-deprenyl may be a promising and selective imaging biomarker of increased MAO-B activity in the human brain and can therefore serve as a prospective PET tracer targeting neuroinflammation and neurodegeneration. © 2010 Elsevier Ltd All rights reserved.

Bubenyak M.,Semmelweis University | Takacs M.,Semmelweis University | Blazics B.,Semmelweis University | Racz A.,Semmelweis University | And 4 more authors.
Arkivoc | Year: 2010

Rutaecarpine (Evodia rutaecarpa) derivatives were synthesized by bioisosteric replacements of the quinazolone moiety of the pentacyclic system with benzothiadiazine 1,1-dioxide. Syntheses were performed efficiently by formation of phenylhydrazones via active methylene group transformations of pyrrolo-and pyrido[1,2-b]1,2,4-benzothiadiazine 5,5-dioxides, and subsequent Fischer-indolization. Preliminary testing of compound 3 showed cytotoxic activity against HeLa cells and apoptosis inducing effect. © ARKAT-USA, Inc.

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