Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies

Document Type

Article

Publication Date

5-15-2025

Publication Title

Molecules

Abstract

The membrane channel protein Panx1 is a promising therapeutic target since its involvement was demonstrated in a variety of pathologies such as neuropathic pain, ischemic stroke and cancer. As a continuation of our previous work in this field, we report here the synthesis and biological evaluation of two classes of compounds as Panx1 blockers: 3-carboxy-6-sulphonamidoquinolone derivatives and new Mefloquine analogs. The series of 3-carboxy-6-sulphonamidoquinolones gave interesting results, affording powerful Panx1 channel blockers with 73.2 < I% < 100 at 50 µM. In particular, 12f was a more potent Panx1 blocker than the reference compound CBX (IC(50) = 2.7 µM versus IC(50) = 7.1 µM), and its profile was further investigated in a cell culture model of polycystic kidney disease. Finally, interesting results have been highlighted by new molecular modeling studies.

Medical Subject Headings

Mefloquine; Molecular Docking Simulation; Humans; Nerve Tissue Proteins; Structure-Activity Relationship; Connexins; Animals; Quinolones; Molecular Structure

PubMed ID

40430343

Volume

30

Issue

10

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