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

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dc.contributor.authorTorres-Fuentes, Cristina
dc.contributor.authorPastor-Cavada, Elena
dc.contributor.authorCano, Rafael
dc.contributor.authorKandil, Dalia
dc.contributor.authorShanahan, Rachel
dc.contributor.authorJuan, Rocio
dc.contributor.authorShaban, Hamdy
dc.contributor.authorMcGlacken, Gerard P.
dc.contributor.authorSchellekens, Harriƫt
dc.contributor.funderUniversidad de Sevilla
dc.contributor.funderIrish Research Council for Science, Engineering and Technology
dc.contributor.funderScience Foundation Ireland
dc.date.accessioned2018-09-20T15:53:43Z
dc.date.available2018-09-20T15:53:43Z
dc.date.issued2018
dc.description.abstractCachexia 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.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid1605
dc.identifier.citationTorres-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/ijms19061605en
dc.identifier.doi10.3390/ijms19061605
dc.identifier.endpage15
dc.identifier.issn1422-0067
dc.identifier.issued6
dc.identifier.journaltitleInternational Journal of Molecular Scienceen
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/6838
dc.identifier.volume19
dc.language.isoenen
dc.publisherMDPIen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IP/1315/IE/The Direct Arylation of Pyrones, Coumarins, Pyridones and Quinolones/
dc.relation.urihttp://www.mdpi.com/1422-0067/19/6/1605
dc.rightsĀ© 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.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGhrelinen
dc.subjectQuinolonesen
dc.subjectCachexiaen
dc.subjectGHS-R1aen
dc.titleQuinolones modulate ghrelin receptor signaling: potential for a novel small molecule scaffold in the treatment of cachexiaen
dc.typeArticle (peer-reviewed)en
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