Phenylpyridine-2-ylguanidines and rigid mimetics as novel inhibitors of TNFα overproduction: Beneficial action in models of neuropathic pain and of acute lung inflammation.
Fiche publication
Date publication
mars 2018
Journal
European journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VILLA Pascal
Tous les auteurs :
Bollenbach M, Salvat E, Daubeuf F, Wagner P, Yalcin I, Humo M, Letellier B, Becker LJ, Bihel F, Bourguignon JJ, Villa P, Obrecht A, Frossard N, Barrot M, Schmitt M
Lien Pubmed
Résumé
4-phenylpyridin-2-yl-guanidine (5b): a new inhibitor of the overproduction of pro-inflammatory cytokines (TNFα and Il1β) was identified from a high-throughput screening of a chemical library on human peripheral blood mononuclear cells (PBMCs) after LPS stimulation. Derivatives, homologues and rigid mimetics of 5b were designed and synthesized, and their cytotoxicity and ability to inhibit TNFα overproduction were evaluated. Among them, compound 5b and its mimetic 12 (2-aminodihydroquinazoline) showed similar inhibitory activities, and were evaluated in vivo in models of lung inflammation and neuropathic pain in mice. In particular, compound 12 proved to be active (5 mg/kg, ip) in both models.
Mots clés
Acute Lung Injury, drug therapy, Animals, Anti-Inflammatory Agents, Non-Steroidal, chemical synthesis, Guanidines, chemical synthesis, Humans, Inflammation, drug therapy, Models, Biological, Neuralgia, drug therapy, Tumor Necrosis Factor-alpha, antagonists & inhibitors
Référence
Eur J Med Chem. 2018 Mar 10;147:163-182