RT Journal Article T1 Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis. A1 Ezzanad, Abdellah A1 Gomez-Oliva, Ricardo A1 Escobar-Montaño, Felipe A1 Diez-Salguero, Monica A1 Geribaldi-Doldan, Noelia A1 Dominguez-Garcia, Samuel A1 Botubol-Ares, Jose Manuel A1 Reyes, Carolina de Los A1 Duran-Patron, Rosa A1 Nunez-Abades, Pedro A1 Macias-Sanchez, Antonio J A1 Castro, Carmen A1 Hernandez-Galan, Rosario 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 (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. PB American Chemical Society YR 2021 FD 2021-05-04 LK http://hdl.handle.net/10668/17742 UL http://hdl.handle.net/10668/17742 LA en NO Ezzanad 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. NO This 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”. DS RISalud RD Apr 9, 2025