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

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 21; p. 6583
• Main Authors: Crocetti, Letizia, Vergelli, Claudia, Guerrini, Gabriella, Giovannoni, Maria Paola, Kirpotina, Liliya N, Khlebnikov, Andrei I, Ghelardini, Carla, Di Cesare Mannelli, Lorenzo, Lucarini, Elena, Schepetkin, Igor A, Quinn, Mark T
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.10.2021; MDPI
• Subjects: Administration, Oral; Agonists; Animal models; Animals; Antigens; Apoptosis; Arthritis; Arthritis, Rheumatoid - chemically induced; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Biological effects; Cartilage; Cytokines; Drug dosages; Drug therapy; Formyl peptide receptors; Freund's Adjuvant; Humans; Inflammation; Inflammatory diseases; Ligands; Male; molecular docking; Molecular modelling; Molecular Structure; Neutrophils; Pathogenesis; Peptides; Pharmacology; Pyridines - administration & dosage; Pyridines - chemistry; Pyridines - pharmacology; pyridinone; Rats; Rats, Sprague-Dawley; Receptors, Formyl Peptide - agonists; Rheumatoid arthritis; Side effects; Tumor Cells, Cultured; agonists; molecular docking; pyridinone; formyl peptide receptors; rheumatoid arthritis
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26216583

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 , the FPR2 agonist , and the pyridine derivative 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 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.