Targeting TRPA1 with Novel Synthetic Compounds Based on Different Scaffolds to Reduce Acute and Chronic Pain

International Journal of Molecular Sciences 2026 Open access

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Authors: Alessia Agata Corallo, Samuele Maramai, Carlotta Noli, Marco Paolino, Antonella Brizzi, Alessia Ligresti, Marco Allarà, Luciano De Petrocellis, Rosa Maria Vitale, Aniello Schiano Moriello, Carmela Belardo, Rosmara Infantino
+3 more Sabatino Maione, Claudia Mugnaini, Federico Corelli
DOI: 10.3390/ijms27041716
Cited by: 1
References: 61

Abstract

The transient receptor potential ankyrin 1 (TRPA1) channel is a nonselective cation channel that detects noxious stimuli. Due to its role in acute and chronic pain transmission, interest in this receptor as a potential therapeutic target has grown. Among the natural compounds tested, δ-sanshool proved to be a promising modulator of TRPA1 due to its interaction with specific receptor cysteines. Starting from this polyunsaturated amide, we designed and prepared a small library of derivatives in which different amide heads were introduced and the length of the unsaturated chain was changed. The newly synthesized compounds were tested in vitro, and the results were rationalized by a molecular docking approach. Two of them, characterized by an agonist profile, were evaluated in vivo in the formalin-induced nociceptive response test, exhibiting promising analgesic properties.

Fields of Study & Subjects

Ion Channels and Receptors Magnolia and Illicium research Pain Mechanisms and Treatments

Publication details

Journal / source
International Journal of Molecular Sciences
Publisher
MDPI AG
Volume
27
Issue
4
Pages
1716–1716
Publication date
10 February 2026
Language
EN