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Sirtuin 1-Activating Compounds: Discovery of a Class of Thiazole-Based Derivatives.
Bononi, Giulia; Citi, Valentina; Lapillo, Margherita; Martelli, Alma; Poli, Giulio; Tuccinardi, Tiziano; Granchi, Carlotta; Testai, Lara; Calderone, Vincenzo; Minutolo, Filippo.
  • Bononi G; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
  • Citi V; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
  • Lapillo M; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
  • Martelli A; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
  • Poli G; Center for Instrument Sharing of the University of Pisa (CISUP), Lungarno Pacinotti 43, 56126 Pisa, Italy.
  • Tuccinardi T; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
  • Granchi C; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
  • Testai L; Center for Instrument Sharing of the University of Pisa (CISUP), Lungarno Pacinotti 43, 56126 Pisa, Italy.
  • Calderone V; Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
  • Minutolo F; Center for Instrument Sharing of the University of Pisa (CISUP), Lungarno Pacinotti 43, 56126 Pisa, Italy.
Molecules ; 27(19)2022 Oct 03.
Article en En | MEDLINE | ID: mdl-36235072
ABSTRACT
Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase implicated in various biological and pathological processes, including cancer, diabetes, and cardiovascular diseases. In recent years, SIRT1-activating compounds have been demonstrated to exert cardioprotective effects. Therefore, this enzyme has become a feasible target to treat cardiovascular diseases, and many SIRT1 activators, of a natural or synthetic origin, have been identified. In the present work, we developed thiazole-based SIRT1 activators, which showed remarkably higher SIRT1 activation potencies compared with those of the reference compound resveratrol when tested in enzymatic assays. Thiazole 8, a representative compound of this series, was also subjected to further pharmacological investigations, where it was proven to reduce myocardial damage induced by an in vivo occlusion/reperfusion event, thus confirming its cardioprotective properties. In addition, the cardioprotective effect of compound 8 was significantly higher than that of resveratrol. Molecular modeling studies suggest the binding mode of these derivatives within SIRT1 in the presence of the p53-AMC peptide. These promising results could pave the way to further expand and optimize this chemical class of new and potent SIRT1 activators as potential cardioprotective agents.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Estilbenos / Enfermedades Cardiovasculares Límite: Humans Idioma: En Año: 2022 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Estilbenos / Enfermedades Cardiovasculares Límite: Humans Idioma: En Año: 2022 Tipo del documento: Article