Publication: Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis.
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Identifiers
Date
2021-05-04
Authors
Ezzanad, Abdellah
Gomez-Oliva, Ricardo
Escobar-Montaño, Felipe
Diez-Salguero, Monica
Geribaldi-Doldan, Noelia
Dominguez-Garcia, Samuel
Botubol-Ares, Jose Manuel
Reyes, Carolina de Los
Duran-Patron, Rosa
Nunez-Abades, Pedro
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
American Chemical Society
Abstract
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.
Description
MeSH Terms
Animals
Cell proliferation
Mice
Neural stem cells
Neurogenesis
Phorbol esters
Transforming growth factor alpha
Cell proliferation
Mice
Neural stem cells
Neurogenesis
Phorbol esters
Transforming growth factor alpha
DeCS Terms
Células-madre neurales
Factor de crecimiento transformador alfa
Neurogénesis
Proliferación celular
Ratones
Ésteres del forbol
Factor de crecimiento transformador alfa
Neurogénesis
Proliferación celular
Ratones
Ésteres del forbol
CIE Terms
Keywords
Citation
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.