Quinolones modulate ghrelin receptor signaling: potential for a novel small molecule scaffold in the treatment of cachexia

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dc.contributor.author Torres-Fuentes, Cristina
dc.contributor.author Pastor-Cavada, Elena
dc.contributor.author Cano, Rafael
dc.contributor.author Kandil, Dalia
dc.contributor.author Shanahan, Rachel
dc.contributor.author Juan, Rocio
dc.contributor.author Shaban, Hamdy
dc.contributor.author McGlacken, Gerard P.
dc.contributor.author Schellekens, Harriët
dc.date.accessioned 2018-09-20T15:53:43Z
dc.date.available 2018-09-20T15:53:43Z
dc.date.issued 2018
dc.identifier.citation Torres-Fuentes, C., Pastor-Cavada, E., Cano, R., Kandil, D., Shanahan, R., Juan, R., Shaban, H., McGlacken, G. and Schellekens, H. (2018) 'Quinolones modulate ghrelin receptor signaling: potential for a novel small molecule scaffold in the treatment of cachexia', International Journal of Molecular Sciences, 19(6), 1605 (15pp). doi: 10.3390/ijms19061605 en
dc.identifier.volume 19
dc.identifier.issued 6
dc.identifier.startpage 1
dc.identifier.endpage 15
dc.identifier.issn 1422-0067
dc.identifier.uri http://hdl.handle.net/10468/6838
dc.identifier.doi 10.3390/ijms19061605
dc.description.abstract Cachexia is a metabolic wasting disorder characterized by progressive weight loss, muscle atrophy, fatigue, weakness, and appetite loss. Cachexia is associated with almost all major chronic illnesses including cancer, heart failure, obstructive pulmonary disease, and kidney disease and significantly impedes treatment outcome and therapy tolerance, reducing physical function and increasing mortality. Current cachexia treatments are limited and new pharmacological strategies are needed. Agonists for the growth hormone secretagogue (GHS-R1a), or ghrelin receptor, prospectively regulate the central regulation of appetite and growth hormone secretion, and therefore have tremendous potential as cachexia therapeutics. Non-peptide GHS-R1a agonists are of particular interest, especially given the high gastrointestinal degradation of peptide-based structures, including that of the endogenous ligand, ghrelin, which has a half-life of only 30 min. However, few compounds have been reported in the literature as non-peptide GHS-R1a agonists. In this paper, we investigate the in vitro potential of quinolone compounds to modulate the GHS-R1a in both transfected human cells and mouse hypothalamic cells. These chemically synthesized compounds demonstrate a promising potential as GHS-R1a agonists, shown by an increased intracellular calcium influx. Further studies are now warranted to substantiate and exploit the potential of these novel quinolone-based compounds as orexigenic therapeutics in conditions of cachexia and other metabolic and eating disorders. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher MDPI en
dc.relation.uri http://www.mdpi.com/1422-0067/19/6/1605
dc.rights © 2018, the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject Ghrelin en
dc.subject Quinolones en
dc.subject Cachexia en
dc.subject GHS-R1a en
dc.title Quinolones modulate ghrelin receptor signaling: potential for a novel small molecule scaffold in the treatment of cachexia en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Harriet Schellekens, Anatomy and Neuroscience, University College Cork, Cork, Ireland. +353-21-490-3000 Email: h.schellekens@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Universidad de Sevilla
dc.contributor.funder Irish Research Council for Science, Engineering and Technology
dc.contributor.funder Science Foundation Ireland
dc.description.status Peer reviewed en
dc.identifier.journaltitle International Journal of Molecular Science en
dc.internal.IRISemailaddress h.schellekens@ucc.ie en
dc.identifier.articleid 1605
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IP/1315/IE/The Direct Arylation of Pyrones, Coumarins, Pyridones and Quinolones/


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© 2018, the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Except where otherwise noted, this item's license is described as © 2018, the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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