Publication:
Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis.

dc.contributor.authorEzzanad, Abdellah
dc.contributor.authorGomez-Oliva, Ricardo
dc.contributor.authorEscobar-Montaño, Felipe
dc.contributor.authorDiez-Salguero, Monica
dc.contributor.authorGeribaldi-Doldan, Noelia
dc.contributor.authorDominguez-Garcia, Samuel
dc.contributor.authorBotubol-Ares, Jose Manuel
dc.contributor.authorReyes, Carolina de Los
dc.contributor.authorDuran-Patron, Rosa
dc.contributor.authorNunez-Abades, Pedro
dc.contributor.authorMacias-Sanchez, Antonio J
dc.contributor.authorCastro, Carmen
dc.contributor.authorHernandez-Galan, Rosario
dc.contributor.authoraffiliation[Gomez-Oliva, Ricardo] Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
dc.contributor.authoraffiliation[Dominguez-Garcia, Samuel] Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
dc.contributor.authoraffiliation[Botubol-Ares, Jose Manuel] Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
dc.contributor.authoraffiliation[Duran-Patron, Rosa] Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
dc.contributor.authoraffiliation[Macias-Sanchez, Antonio J] Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain. Instituto de Investigación en Biomoléculas (INBIO), Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
dc.contributor.authoraffiliation[Castro, Carmen] Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
dc.contributor.authoraffiliation[Hernandez-Galan, Rosario] Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain. Instituto de Investigación en Biomoléculas (INBIO), Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
dc.contributor.funderMinisterio de Ciencia, Innovacion y Universidades
dc.contributor.funderConsejería de Economia, Conocimiento, Empresas y Universidades
dc.contributor.funderJunta de Andalucia
dc.date.accessioned2023-02-09T11:38:24Z
dc.date.available2023-02-09T11:38:24Z
dc.date.issued2021-05-04
dc.description.abstractA small library of phorbol 12,13-diesters bearing low lipophilicity ester chains was prepared as potential neurogenic agents in the adult brain. They were also used in a targeted UHPLC-HRMS screening of the latex of Euphorbia resinifera. Two new 12-deoxy-16-hydroxyphorbol 13,16-diesters were isolated, and their structures were deduced using two-dimensional NMR spectroscopy and NOE experiments. The ability of natural and synthetic compounds to stimulate transforming growth factor alpha (TFGα) release, to increase neural progenitor cell proliferation, and to stimulate neurogenesis was evaluated. All compounds that facilitated TGFα release promoted neural progenitor cell proliferation. The presence of two acyloxy moieties on the tigliane skeleton led to higher levels of activity, which decreased when a free hydroxyl group was at C-12. Remarkably, the compound bearing isobutyryloxy groups was the most potent on the TGFα assay and at inducing neural progenitor cell proliferation in vitro, also leading to enhanced neurogenesis in vivo when administered intranasally to mice.
dc.description.sponsorshipThis work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (grant nos RTI2018–099908-B-C21 and RTI2018–099908-B-C22 MICINN/FEDER granted to CC and RHG, respectively) and Consejería de Economía, Conocimiento, Empresas y Universidades Junta de Andalucía (grant no FEDER-ANDALUCÍA sol2018–00106647-tra). We thank the “Servicio de experimentación y producción animal (SEPA) de la Universidad de Cádiz” as well as the “Servicios Centrales de apoyo a la investigación en Ciencias de la Salud (SCICS) de la Universidad de Cádiz” and “Servicios centrales de Ciencia y tecnología (SC-ICYT) de la Universidad de Cádiz”.
dc.description.versionSi
dc.identifier.citationEzzanad A, Gómez-Oliva R, Escobar-Montaño F, Díez-Salguero M, Geribaldi-Doldan N, Dominguez-Garcia S, et al. Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis. J Med Chem. 2021 May 13;64(9):6070-6084.
dc.identifier.doi10.1021/acs.jmedchem.1c00156
dc.identifier.essn1520-4804
dc.identifier.pmid33945688
dc.identifier.unpaywallURLhttps://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.1c00156
dc.identifier.urihttp://hdl.handle.net/10668/17742
dc.issue.number9
dc.journal.titleJournal of medicinal chemistry
dc.journal.titleabbreviationJ Med Chem
dc.language.isoen
dc.organizationInstituto de Investigación e Innovación en Ciencias Biomédicas
dc.page.number6070-6084
dc.provenance01-10-24
dc.publisherAmerican Chemical Society
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDRTI2018−099908-B-C21
dc.relation.projectIDRTI2018−099908-B-C22
dc.relation.projectID2018−00106647
dc.relation.publisherversionhttps://pubs.acs.org/doi/10.1021/acs.jmedchem.1c00156
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.decsCélulas-madre neurales
dc.subject.decsFactor de crecimiento transformador alfa
dc.subject.decsNeurogénesis
dc.subject.decsProliferación celular
dc.subject.decsRatones
dc.subject.decsÉsteres del forbol
dc.subject.meshAnimals
dc.subject.meshCell proliferation
dc.subject.meshMice
dc.subject.meshNeural stem cells
dc.subject.meshNeurogenesis
dc.subject.meshPhorbol esters
dc.subject.meshTransforming growth factor alpha
dc.titlePhorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis.
dc.typeResearch article
dc.type.hasVersionVoR
dc.volume.number64
dspace.entity.typePublication

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