RT journal article
T1 Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGF alpha Release and Adult Mouse Neurogenesis
A1 Ezzanad, Abdellah
A1 Gómez Oliva, Ricardo
A1 Escobar Montaño, Felipe
A1 Díez Salguero, Mónica
A1 Geribaldi Doldán, Noelia
A1 Domínguez García, Samuel
A1 Botubol Ares, José Manuel
A1 Reyes Jiménez, Carolina de los
A1 Durán Patrón, Rosa María
A1 Nunez Abades, Pedro
A1 Macías Sánchez, Antonio José
A1 Castro González, Carmen
A1 Hernández Galán, Rosario
A2 BiomedicinaBiotecnología y Salud Pública
A2 Química Orgánica
AB A 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 (TFG alpha) release, to increase neural progenitor cell proliferation, and to stimulate neurogenesis was evaluated. All compounds that facilitated TGF alpha 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 TGF alpha assay and at inducing neural progenitor cell proliferation in vitro, also leading to enhanced neurogenesis in vivo when administered intranasally to mice.
PB AMER CHEMICAL SOC
SN 0022-2623
YR 2021
FD 2021-05-13
LK http://hdl.handle.net/10498/25169
UL http://hdl.handle.net/10498/25169
LA eng
NO This work was supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades (grant nos RTI2018-099908-BC21 and RTI2018-099908-B-C22 MICINN/FEDER granted to CC and RHG, respectively) and Consejeria de Economia, Conocimiento, Empresas y Universidades Junta de Andalucia (grant no FEDER-ANDALUCIA sol2018-00106647-tra). We thank the "Servicio de experimentacion y produccion animal (SEPA) de la Universidad de Cadiz" as well as the "Servicios Centrales de apoyo a la investigacion en Ciencias de la Salud (SCICS) de la Universidad de Cadiz" and "Servicios centrales de Ciencia Cadiz".
DS Repositorio Institucional de la Universidad de Cádiz
RD 08-nov-2026