Trehalose-based neuroprotective autophagy inducers.

Autophagy / drug effects Drug Design Gold / chemistry HeLa Cells Humans Metal Nanoparticles / chemistry Neuroprotective Agents / chemical synthesis Polyethylene Glycols / chemistry Trehalose / analogs & derivatives
Autophagy Chemical probes Nanoparticles Neurodegeneration Prodrugs Trehalose

Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 05 2021
Historique:
received: 30 10 2020
revised: 25 02 2021
accepted: 27 02 2021
pubmed: 12 3 2021
medline: 22 9 2021
entrez: 11 3 2021
Statut: ppublish

Résumé

A small set of trehalose-centered putative autophagy inducers was rationally designed and synthesized, with the aim to identify more potent and bioavailable autophagy inducers than free trehalose, and to acquire information about their molecular mechanism of action. Several robust, high yield routes to key trehalose intermediates and small molecule prodrugs (2-5), putative probes (6-10) and inorganic nanovectors (12a - thiol-PEG-triazole-trehalose constructs 11) were successfully executed, and compounds were tested for their autophagy-inducing properties. While small molecules 2-11 showed no pro-autophagic behavior at sub-millimolar concentrations, trehalose-bearing PEG-AuNPs 12a caused measurable autophagy induction at an estimated 40 μM trehalose concentration without any significant toxicity at the same concentration.

Identifiants

DOI: 10.1016/j.bmcl.2021.127929 PMID: 33705903
pubmed: 33705903
pii: S0960-894X(21)00155-4
doi: 10.1016/j.bmcl.2021.127929
pii:
doi:

Substances chimiques

Neuroprotective Agents 0
Polyethylene Glycols 3WJQ0SDW1A
Gold 7440-57-5
Trehalose B8WCK70T7I

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

127929

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Auteurs

Giulia Assoni (G)

Department of Cellular, Computational And Integrative Biology, (CIBIO), Via Sommarive 9, I-38123 Povo, TN, Italy.

Giulia Frapporti (G)

Department of Cellular, Computational And Integrative Biology, (CIBIO), Via Sommarive 9, I-38123 Povo, TN, Italy.

Eleonora Colombo (E)

Chemistry Department, Università Statale di Milano, Via Golgi 19, I-20133 Milan, Italy.

Davide Gornati (D)

Chemistry Department, Università Statale di Milano, Via Golgi 19, I-20133 Milan, Italy.

Maria Dolores Perez-Carrion (MD)

Unidad Asociada Neurodeath, Departamento de Ciencias Médicas, Universidad de Castilla-La Mancha, Albacete, Spain.

Laura Polito (L)

Istituto di Scienze e Tecnologie Chimiche (SCITEC) "Giulio Natta", Consiglio Nazionale delle Ricerche (CNR), Via C. Golgi 19, I-20133 Milan, Italy and Via G. Fantoli 16/15, I-20138 Milan, Italy.

Pierfausto Seneci (P)

Chemistry Department, Università Statale di Milano, Via Golgi 19, I-20133 Milan, Italy. Electronic address: pierfausto.seneci@unimi.it.

Giovanni Piccoli (G)

Department of Cellular, Computational And Integrative Biology, (CIBIO), Via Sommarive 9, I-38123 Povo, TN, Italy. Electronic address: giovanni.piccoli@unitn.it.

Daniela Arosio (D)

Istituto di Scienze e Tecnologie Chimiche (SCITEC) "Giulio Natta", Consiglio Nazionale delle Ricerche (CNR), Via C. Golgi 19, I-20133 Milan, Italy and Via G. Fantoli 16/15, I-20138 Milan, Italy. Electronic address: daniela.arosio@scitec.cnr.it.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques cellulaires › Autophagie › Trehalose-based neuroprotective autophagy inducers.
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Conception de médicament › Trehalose-based neuroprotective autophagy inducers.
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux lourds › Or › Trehalose-based neuroprotective autophagy inducers.
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HeLa › Trehalose-based neuroprotective autophagy inducers.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Trehalose-based neuroprotective autophagy inducers.
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Nanoparticules métalliques › Trehalose-based neuroprotective autophagy inducers.
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Neuroprotecteurs › Trehalose-based neuroprotective autophagy inducers.
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Polyéthylène glycols › Trehalose-based neuroprotective autophagy inducers.
questionsmedicales.fr › Glucides › Sucres › Diholoside › Tréhalose › Trehalose-based neuroprotective autophagy inducers.