Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, cartilage damage and bone destruction. Although the pharmacological treatment of RA has evolved over the last few years, the new drugs have serious side effects and are very expensive. Thus, the research...

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Autores principales:	Letizia Crocetti, Claudia Vergelli, Gabriella Guerrini, Maria Paola Giovannoni, Liliya N. Kirpotina, Andrei I. Khlebnikov, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Elena Lucarini, Igor A. Schepetkin, Mark T. Quinn
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pyridinone formyl peptide receptors agonists rheumatoid arthritis molecular docking Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/794694ec985b41be98154621c4206a54
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spelling	oai:doaj.org-article:794694ec985b41be98154621c4206a542021-11-11T18:33:43ZPyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis10.3390/molecules262165831420-3049https://doaj.org/article/794694ec985b41be98154621c4206a542021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6583https://doaj.org/toc/1420-3049Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, cartilage damage and bone destruction. Although the pharmacological treatment of RA has evolved over the last few years, the new drugs have serious side effects and are very expensive. Thus, the research has been directed in recent years towards new possible targets. Among these targets, N-formyl peptide receptors (FPRs) are of particular interest. Recently, the mixed FPR1/FPR2 agonist <b>Cpd43</b>, the FPR2 agonist <b>AT-01-KG</b>, and the pyridine derivative <b>AMC3</b> have been shown to be effective in RA animal models. As an extension of this research, we report here a new series of pyridinone derivatives containing the (substituted)phenyl acetamide chain, which was found to be essential for activity, but with different substitutions at position 5 of the scaffold. The biological results were also supported by molecular modeling studies and additional pharmacological tests on <b>AMC3</b> have been performed in a rat model of RA, by repeating the treatments of the animals with 10 mg/kg/day of compound by 1 week.Letizia CrocettiClaudia VergelliGabriella GuerriniMaria Paola GiovannoniLiliya N. KirpotinaAndrei I. KhlebnikovCarla GhelardiniLorenzo Di Cesare MannelliElena LucariniIgor A. SchepetkinMark T. QuinnMDPI AGarticlepyridinoneformyl peptide receptorsagonistsrheumatoid arthritismolecular dockingOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6583, p 6583 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pyridinone formyl peptide receptors agonists rheumatoid arthritis molecular docking Organic chemistry QD241-441
spellingShingle	pyridinone formyl peptide receptors agonists rheumatoid arthritis molecular docking Organic chemistry QD241-441 Letizia Crocetti Claudia Vergelli Gabriella Guerrini Maria Paola Giovannoni Liliya N. Kirpotina Andrei I. Khlebnikov Carla Ghelardini Lorenzo Di Cesare Mannelli Elena Lucarini Igor A. Schepetkin Mark T. Quinn Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis
description	Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, cartilage damage and bone destruction. Although the pharmacological treatment of RA has evolved over the last few years, the new drugs have serious side effects and are very expensive. Thus, the research has been directed in recent years towards new possible targets. Among these targets, N-formyl peptide receptors (FPRs) are of particular interest. Recently, the mixed FPR1/FPR2 agonist <b>Cpd43</b>, the FPR2 agonist <b>AT-01-KG</b>, and the pyridine derivative <b>AMC3</b> have been shown to be effective in RA animal models. As an extension of this research, we report here a new series of pyridinone derivatives containing the (substituted)phenyl acetamide chain, which was found to be essential for activity, but with different substitutions at position 5 of the scaffold. The biological results were also supported by molecular modeling studies and additional pharmacological tests on <b>AMC3</b> have been performed in a rat model of RA, by repeating the treatments of the animals with 10 mg/kg/day of compound by 1 week.
format	article
author	Letizia Crocetti Claudia Vergelli Gabriella Guerrini Maria Paola Giovannoni Liliya N. Kirpotina Andrei I. Khlebnikov Carla Ghelardini Lorenzo Di Cesare Mannelli Elena Lucarini Igor A. Schepetkin Mark T. Quinn
author_facet	Letizia Crocetti Claudia Vergelli Gabriella Guerrini Maria Paola Giovannoni Liliya N. Kirpotina Andrei I. Khlebnikov Carla Ghelardini Lorenzo Di Cesare Mannelli Elena Lucarini Igor A. Schepetkin Mark T. Quinn
author_sort	Letizia Crocetti
title	Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis
title_short	Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis
title_full	Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis
title_fullStr	Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis
title_full_unstemmed	Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis
title_sort	pyridinone derivatives as interesting formyl peptide receptor (fpr) agonists for the treatment of rheumatoid arthritis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/794694ec985b41be98154621c4206a54
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Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis

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