In silico and pharmacological study of N,S-acetal juglone derivatives as inhibitors of the P2X7 receptor-promoted in vitro and in vivo inflammatory response - 29/04/23
Abstract |
Purinergic receptors are transmembrane proteins responsive to extracellular nucleotides and are expressed by several cell types throughout the human body. Among all identified subtypes, the P2×7 receptor has emerged as a relevant target for the treatment of inflammatory disease. Several clinical trials have been conducted to evaluate the effectiveness of P2×7R antagonists. However, to date, no selective antagonist has reached clinical use. In this work, we report the pharmacological evaluation of eleven N, S-acetal juglone derivatives as P2×7R inhibitors. Using in vitro assays and in vivo experimental models, we identified one derivative with promising inhibitory activity and low toxicity. Our in silico studies indicate that the 1,4-naphthoquinone moiety might be a valuable molecular scaffold for the development of novel P2×7R antagonists, as suggested by our previous studies.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | P2X7 receptor (P2X7R) is an ATP-gated ion channel involved in several inflammatory diseases and neuropathic pain. |
• | P2X7R activation triggers several pro-inflammatory mechanisms, such as NLRP3 inflammasome assembly and release of IL-1β. |
• | Despite the key role of P2X7R in inflammatory disorders, no inhibitor is approved for clinical use yet. |
• | Juglone-derived N,S-acetal compounds showed good in vitro and in vivo P2X7R inhibitory activity. |
• | In silico studies corroborates that 1,4-naphthoquinones might be valuable synthetic platforms for novel P2X7 antagonists. |
Keywords : Purinergic receptors, P2X7R, ATP, Inflammation, Drug, Naphthoquinone
Plan
Vol 162
Article 114608- juin 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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