Abstract: Pannexins are an interesting new target in medicinal chemistry, as they are involved in many pathologies such as epilepsy, ischemic stroke, cancer and Parkinson’s disease, as well as in neuropathic pain. They are a family of membrane channel proteins consisting of three members, Panx-1, Panx-2 and Panx-3, and are expressed in vertebrates. In the present study, as a continuation of our research in this field, we report the design, synthesis and pharmacological evaluation of new quinoline-based Panx-1 blockers. The most relevant compounds 6f and 6g show an IC50 = 3 and 1.5 M, respectively, and are selective Panx-1 blockers. Finally, chemical stability, molecular modelling and X-ray crystallography studies have been performed providing useful information for the realization of the project.

Design, Synthesis and Pharmacological Evaluation of New Quinoline-Based Panx-1 Channel Blockers / Crocetti, Letizia; Giovannoni, Maria Paola; Guerrini, Gabriella; Lamanna, Silvia; Melani, Fabrizio; Bartolucci, Gian Luca; Pallecchi, Marco; Paoli, Paola; Lippi, Martina; Wang, Junjie; Dahl, Gerhard. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - ELETTRONICO. - 24:(2023), pp. 1-23. [10.3390/ijms24032022]

Design, Synthesis and Pharmacological Evaluation of New Quinoline-Based Panx-1 Channel Blockers

Crocetti, Letizia;Giovannoni, Maria Paola;Guerrini, Gabriella
;
Lamanna, Silvia;Melani, Fabrizio;Bartolucci, Gian Luca;Pallecchi, Marco;Paoli, Paola;Lippi, Martina;
2023

Abstract

Abstract: Pannexins are an interesting new target in medicinal chemistry, as they are involved in many pathologies such as epilepsy, ischemic stroke, cancer and Parkinson’s disease, as well as in neuropathic pain. They are a family of membrane channel proteins consisting of three members, Panx-1, Panx-2 and Panx-3, and are expressed in vertebrates. In the present study, as a continuation of our research in this field, we report the design, synthesis and pharmacological evaluation of new quinoline-based Panx-1 blockers. The most relevant compounds 6f and 6g show an IC50 = 3 and 1.5 M, respectively, and are selective Panx-1 blockers. Finally, chemical stability, molecular modelling and X-ray crystallography studies have been performed providing useful information for the realization of the project.
2023
24
1
23
Crocetti, Letizia; Giovannoni, Maria Paola; Guerrini, Gabriella; Lamanna, Silvia; Melani, Fabrizio; Bartolucci, Gian Luca; Pallecchi, Marco; Paoli, Paola; Lippi, Martina; Wang, Junjie; Dahl, Gerhard
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1297899
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