KOPS - Das Institutionelle Repositorium der Universität Konstanz

Functional assay and structure–activity relationships of new third-generation P-glycoprotein inhibitors

Functional assay and structure–activity relationships of new third-generation P-glycoprotein inhibitors

Zitieren

Dateien zu dieser Ressource

Dateien Größe Format Anzeige

Zu diesem Dokument gibt es keine Dateien.

MÜLLER, Henrik, Ilza K. PAJEVA, Christoph GLOBISCH, Michael WIESE, 2008. Functional assay and structure–activity relationships of new third-generation P-glycoprotein inhibitors. In: Bioorganic & Medicinal Chemistry. 16(5), pp. 2448-2462. ISSN 0968-0896. eISSN 1464-3391. Available under: doi: 10.1016/j.bmc.2007.11.057

@article{Muller2008-03Funct-38225, title={Functional assay and structure–activity relationships of new third-generation P-glycoprotein inhibitors}, year={2008}, doi={10.1016/j.bmc.2007.11.057}, number={5}, volume={16}, issn={0968-0896}, journal={Bioorganic & Medicinal Chemistry}, pages={2448--2462}, author={Müller, Henrik and Pajeva, Ilza K. and Globisch, Christoph and Wiese, Michael} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/38225"> <dc:contributor>Wiese, Michael</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/38225"/> <dc:contributor>Pajeva, Ilza K.</dc:contributor> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-03-30T09:27:27Z</dc:date> <dc:creator>Müller, Henrik</dc:creator> <dc:creator>Globisch, Christoph</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-03-30T09:27:27Z</dcterms:available> <dc:creator>Wiese, Michael</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:language>eng</dc:language> <dcterms:title>Functional assay and structure–activity relationships of new third-generation P-glycoprotein inhibitors</dcterms:title> <dcterms:abstract xml:lang="eng">Twenty-eight compounds, including 24 structurally related derivatives of tariquidar synthesized in our laboratory, and four XR compounds, reported by Xenova group Ltd, were investigated by the Hoechst 33342 and Calcein AM functional assays for estimation of their inhibitory effects on the transport activity of P-glycoprotein (P-gp). A high correlation between the effects obtained in both assays was observed at the substrate concentrations used. The analyses of kinetics data from experiments at different substrate concentrations revealed non-competitive inhibition in the Calcein AM assay and competitive inhibition in the Hoechst 33342 assay. The 3D structures of the compounds were further aligned on Hoechst 33342 using flexible and pharmacophore alignments. The results suggested that inhibitors could interact with the H-binding site of P-gp and this could potentially be achieved by different ways of binding. The best 3D-QSAR models, generated by CoMFA and CoMSIA, yielded an internal predictive squared correlation coefficient higher than 0.8 and included electrostatic, steric, hydrogen bond acceptor, and hydrophobic fields. Validation of the models on an external test set of 30 XR compounds gave predictive squared correlation coefficients of up to 0.66. An excellent correspondence between the experimental and modeled activities of the test compounds was observed. The models can be used for prediction and rational design of new P-gp inhibitors.</dcterms:abstract> <dc:contributor>Müller, Henrik</dc:contributor> <dcterms:issued>2008-03</dcterms:issued> <dc:creator>Pajeva, Ilza K.</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Globisch, Christoph</dc:contributor> </rdf:Description> </rdf:RDF>

Das Dokument erscheint in:

KOPS Suche


Stöbern

Mein Benutzerkonto