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Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis.
Ezzanad, Abdellah; Gómez-Oliva, Ricardo; Escobar-Montaño, Felipe; Díez-Salguero, Mónica; Geribaldi-Doldan, Noelia; Dominguez-Garcia, Samuel; Botubol-Ares, José Manuel; Reyes, Carolina de Los; Durán-Patrón, Rosa; Nunez-Abades, Pedro; Macías-Sánchez, Antonio J; Castro, Carmen; Hernández-Galán, Rosario.
Afiliação
  • Ezzanad A; Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
  • Gómez-Oliva R; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, 11002 Cádiz, Spain.
  • Escobar-Montaño F; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
  • Díez-Salguero M; Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
  • Geribaldi-Doldan N; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, 11002 Cádiz, Spain.
  • Dominguez-Garcia S; Departamento de Anatomía y Embriología Humanas, Universidad de Cádiz, 11002 Cádiz, Spain.
  • Botubol-Ares JM; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, 11002 Cádiz, Spain.
  • Reyes CL; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
  • Durán-Patrón R; Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
  • Nunez-Abades P; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
  • Macías-Sánchez AJ; Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
  • Castro C; Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
  • Hernández-Galán R; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), 11009 Cádiz, Spain.
J Med Chem ; 64(9): 6070-6084, 2021 05 13.
Article em En | MEDLINE | ID: mdl-33945688
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ésteres de Forbol / Fator de Crescimento Transformador alfa / Neurogênese Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ésteres de Forbol / Fator de Crescimento Transformador alfa / Neurogênese Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article