Work

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

Year: 2025

Type: article

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 (IC50 = 2.7 µM versus IC50 = 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.

Source: Molecules

DOI: 10.3390/molecules30102171

Authors: Letizia Crocetti, Maria Paola Giovannoni, Tengis S. Pavlov, Veniamin Ivanov, Fabrizio Melani, Gabriella Guerrini

Institutions: University of Florence, Henry Ford Health, Wayne State University, Henry Ford Hospital

Language: English

Topic: Adenosine and Purinergic Signaling

Subfield: Physiology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258