Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies
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 o...
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2025-05-01
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| author | Letizia Crocetti Maria Paola Giovannoni Tengis S. Pavlov Veniamin Ivanov Fabrizio Melani Gabriella Guerrini |
| author_facet | Letizia Crocetti Maria Paola Giovannoni Tengis S. Pavlov Veniamin Ivanov Fabrizio Melani Gabriella Guerrini |
| author_sort | Letizia Crocetti |
| collection | DOAJ |
| description | 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, <b>12f</b> was a more potent Panx1 blocker than the reference compound CBX (IC<sub>50</sub> = 2.7 µM versus IC<sub>50</sub> = 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. |
| format | Article |
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| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-345ce0cecaca4eeabd84d1a1d1cd3c542025-08-20T01:56:38ZengMDPI AGMolecules1420-30492025-05-013010217110.3390/molecules30102171Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture StudiesLetizia Crocetti0Maria Paola Giovannoni1Tengis S. Pavlov2Veniamin Ivanov3Fabrizio Melani4Gabriella Guerrini5Neurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, ItalyNeurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, ItalyDivision of Hypertension and Vascular Research, Henry Ford Health & Wayne State University, 6135 Woodward Ave, Detroit, MI 48202, USADivision of Hypertension and Vascular Research, Henry Ford Health & Wayne State University, 6135 Woodward Ave, Detroit, MI 48202, USANeurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, ItalyNeurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, ItalyThe 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, <b>12f</b> was a more potent Panx1 blocker than the reference compound CBX (IC<sub>50</sub> = 2.7 µM versus IC<sub>50</sub> = 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.https://www.mdpi.com/1420-3049/30/10/2171Panx1channel blockersquinolonespatch clampmolecular dockingmultiple linear regression (MLR) |
| spellingShingle | Letizia Crocetti Maria Paola Giovannoni Tengis S. Pavlov Veniamin Ivanov Fabrizio Melani Gabriella Guerrini Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies Molecules Panx1 channel blockers quinolones patch clamp molecular docking multiple linear regression (MLR) |
| title | Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies |
| title_full | Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies |
| title_fullStr | Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies |
| title_full_unstemmed | Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies |
| title_short | Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies |
| title_sort | synthesis of 3 carboxy 6 sulfamoylquinolones and mefloquine based compounds as panx1 blockers molecular docking electrophysiological and cell culture studies |
| topic | Panx1 channel blockers quinolones patch clamp molecular docking multiple linear regression (MLR) |
| url | https://www.mdpi.com/1420-3049/30/10/2171 |
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