Portal de investigación
Synthesis of a new 2-prenylated quinoline as potential drug for metabolic syndrome with pan-PPAR activity and anti-inflammatory effects.
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Villarroel-Vicente, C
- Zibar, K
- Schiel, MA
- Ferri, J
- Hennuyer, N
- Enriz, RD
- Staels, B
Grupos y Plataformas de I+D+i
Abstract
We have previously reported the total synthesis and structure-activity relationships (SAR) of 2-prenylated benzopyrans with PPAR agonist activity. Herein, we have described the synthesis and PPAR activity of 2-prenylated benzopyrans and 2-prenylated quinolines. The benzopyran nucleus was generated via enamine-catalyzed Kabbe condensation, and the quinoline nucleus via Friedländer condensation. Results demonstrated that both benzopyran (5a) and quinoline (4b) derivatives bearing a ?,d-unsaturated ester displayed a pan-PPAR agonism. They were full PPARa agonists, but showed different preferences for PPAR? and PPARß/d activation. It was noteworthy that quinoline 4b displayed full hPPARa activation (2-fold than WY-14,643), weak PPARß/d and partial PPAR? activation. In addition, quinoline 4b showed anti-inflammatory effects on macrophages by reducing LPS-induced expression of both MCP-1 and IL-6. Therefore, 4b emerges as a first-in-class promising hit compound for the development of potential therapeutics aimed at treating metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD), and its associated cardiovascular comorbidities.
Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 0960-894X, 1464-3405
- Tipo:
- Article
- Páginas:
- 129770-129770
- PubMed:
- 38677560
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS PERGAMON-ELSEVIER SCIENCE LTD
Citas Recibidas en Web of Science: 3
Documentos
- No hay documentos
Filiaciones
Keywords
- 2-Prenylated benzopyrans; 2-Prenylated quinolines; Anti-inflammatory agents; MAFLD; Metabolic syndrome; PPAR
Financiación
Proyectos y Estudios Clínicos
FI19/00153 (PFIS) CARLOS VILLARROEL (209/207): CONTRATOS PREDOCTORALES DE FORMACIÓN EN INVESTIGACIÓN EN SALUD. Acción Estratégica en Salud 2019.
Investigador Principal: NURIA CABEDO ESCRIG
FI19/00153 . INSTITUTO SALUD CARLOS III
CONTRATOS MIGUEL SERVET TIPO II
Investigador Principal: NURIA CABEDO ESCRIG
CPII20/00010 . INSTITUTO SALUD CARLOS III
Desarrollo de nuevos moduladores multidiana de receptores nucleares y biomarcadores lipídicos para el tratamiento del síndrome metabólico y las comorbilidades asociadas.
Investigador Principal: NURIA CABEDO ESCRIG
PI21/02045 . INSTITUTO SALUD CARLOS III . 2022
Cita
Villarroel C,García A,Zibar K,Schiel MA,Ferri J,Hennuyer N,Enriz RD,Staels B,Cortes D,Cabedo N. Synthesis of a new 2-prenylated quinoline as potential drug for metabolic syndrome with pan-PPAR activity and anti-inflammatory effects. Bioorg. Med. Chem. Lett. 2024. 106. p. 129770-129770. IF:2,200. (2).
Synthesis of a new 2-prenylated quinoline as potential drug for metabolic syndrome with pan-PPAR activity and anti-inflammatory effects. Villarroel C, García A, Zibar K, Schiel MA, Ferri J, Hennuyer N, Enriz RD et al. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 2024 julio 01. 106129770-129770. DOI:10.1016/j.bmcl.2024.129770. PMID:38677560.
