Discovery of flavone-derivatives as the new skeleton of transient receptor potential vanilloid 3 channel antagonists

Bioorg Med Chem Lett. 2023 Dec 6:129577. doi: 10.1016/j.bmcl.2023.129577. Online ahead of print.ABSTRACTTransient receptor potential vanilloid 3 (TRPV3) channel is a temperature-sensitive and Ca2+-permeable nonselective cation channel, which is abundantly expressed in skin keratinocyte and plays an important role in skin homeostasis and repair. However, only a few TRPV3 inhibitors were reported. Few selective and potent modulators of the TRPV3 channel have hindered the progress of the investigation and clinical application. TRPV3 channel research still faces challenges and requires the new inhibitors. Flavonoids are a kind of natural compounds with various biological and pharmacological activities including anti-inflammatory and anti allergic effects, which is associated with some physiological effects mediated by TRPV3 channel. Herein, our group designed and synthesized a range of flavone derivatives, and investigated their inhibitory properties on the human TRPV3 channel by electrophysiology technique. Then, we identified a new potent TRPV3 antagonist 2d with IC50 of 0.62 μM. It also showed good selectivity on TRPV1, TRPV4, TRPA1 and TRPM8.PMID:38065293 | DOI:10.1016/j.bmcl.2023.129577

Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Lili Wang Ling Zhang Rongfeng Liu Yimei Xu Zhifeng Tang Congxiao Zhang Zhongyin Zhang Source Type: research