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2D- and 3D-QSAR studies of a series of benzopyranes and benzopyrano[3,4b][1,4]-oxazines as inhibitors of the multidrug transporter P-glycoprotein

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dc.contributor.author Jabeen, Ishrat
dc.contributor.author Wetwitayaklung, Penpun
dc.contributor.author Chiba, Peter
dc.contributor.author Pastor Maeso, Manuel
dc.contributor.author Ecker, Gerhard F.
dc.date.accessioned 2015-11-30T15:56:13Z
dc.date.available 2015-11-30T15:56:13Z
dc.date.issued 2013
dc.identifier.citation Jabeen I, Wetwitayaklung P, Chiba P, Pastor M, Ecker GF. 2D- and 3D-QSAR studies of a series of benzopyranes and benzopyrano[3,4b][1,4]-oxazines as inhibitors of the multidrug transporter P-glycoprotein. Journal of computer-aided molecular design. 2013. 27(2): 161-171. DOI 10.1007/s10822-013-9635-9
dc.identifier.issn 0920-654X
dc.identifier.uri http://hdl.handle.net/10230/25269
dc.description.abstract The ATP-binding cassette efflux transporter P-glycoprotein (P-gp) is notorious for contributing to multidrug resistance in antitumor therapy. Due to its expression in many blood-organ barriers, it also influences the pharmacokinetics of drugs and drug candidates and is involved in drug/drug- and drug/nutrient interactions. However, due to lack of structural information the molecular basis of ligand/transporter interaction still needs to be elucidated. Towards this goal, a series of Benzopyranes and Benzopyrano[3,4b][1,4]oxazines have been synthesized and pharmacologically tested for their ability to inhibit P-gp mediated daunomycin efflux. Both quantitative structure-activity relationship (QSAR) models using simple physicochemical and novel GRID-independent molecular descriptors (GRIND) were established to shed light on the structural requirements for high P-gp inhibitory activity. The results from 2D-QSAR showed a linear correlation of vdW surface area (Å(2)) of hydrophobic atoms with the pharmacological activity. GRIND (3D-QSAR) studies allowed to identify important mutual distances between pharmacophoric features, which include one H-bond donor, two H-bond acceptors and two hydrophobic groups as well as their distances from different steric hot spots of the molecules. Activity of the compounds particularly increases with increase of the distance of an H-bond donor or a hydrophobic feature from a particular steric hot spot of the benzopyrane analogs.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher SpringerOpen
dc.relation.ispartof Journal of computer-aided molecular design. 2013. 27(2): 161-171
dc.rights © 2013 The Author(s). This is an open access article distributed under the creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subject.other Molècules Models
dc.subject.other Antibiòtics
dc.title 2D- and 3D-QSAR studies of a series of benzopyranes and benzopyrano[3,4b][1,4]-oxazines as inhibitors of the multidrug transporter P-glycoprotein
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1007/s10822-013-9635-9
dc.subject.keyword P-glycoprotein
dc.subject.keyword Multidrug resistance
dc.subject.keyword QSAR
dc.subject.keyword GRIND
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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