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Ion Channels as Therapeutic Target: Drug Design and Pharmacological Investigation 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 2179

Special Issue Editors


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Dipartimento NEUROFARBA, Università degli Studi di Firenze, Via U. Schiff, 6, 50019 Polo Scientifico, Sesto Fiorentino, Firenze, Italy
Interests: heterocyclic nitrogen compounds; pyrazolo condensed compounds; synthesis; GABAA receptor subtype; human neutrophil elastase inhibitors; medicinal chemistry
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Guest Editor
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Firenze, via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy
Interests: medicinal chemistry; organic synthesis; heterocycles; GABAA subtype receptors; HNE inhibitors; FPR

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue “Ion Channels as Therapeutic Target: Drug Design and Pharmacological Investigation”.

The targeting of ion channels represents a strategy for the treatment of several pathologies since they are responsible for ion fluxes across membranes and contribute to maintaining cellular functions in central and peripheral tissues. The ion channels include two principal types of membrane proteins:

  1. The ligand-gated ion channels (LGICs), opened by neurotransmitters or ligands that bind the orthosteric or allosteric sites involved in the overall fast synaptic transmission in the nervous system;
  2. Voltage-gated ion channels, opened or closed by a change in the electrical gradient across the membrane.

Ion channels are very intriguing targets, and the development of new techniques elucidating the structures of these channels (e.g., cryo-EM) contributes to the design of new potential therapeutic agents for the treatment of neurological and neurodegenerative diseases, cancer, metabolic syndrome, and pain.

This Special Issue, titled ‘Ion Channels as Therapeutic Target: Drug Design and Pharmacological Investigation’, aims to collect contributions related to the drug design, molecular modeling, pharmacological investigation, and therapeutic applications of ion channel ligands.

Dr. Gabriella Guerrini
Dr. Maria P. Giovannoni
Guest Editors

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Published Papers (2 papers)

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Research

14 pages, 3845 KiB  
Article
State-Dependent Blockade of Dorsal Root Ganglion Voltage-Gated Na+ Channels by Anethole
by Luiz Moreira-Junior, Jose Henrique Leal-Cardoso, Antonio Carlos Cassola and Joao Luis Carvalho-de-Souza
Int. J. Mol. Sci. 2024, 25(2), 1034; https://doi.org/10.3390/ijms25021034 - 14 Jan 2024
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Abstract
Anethole is a phenolic compound synthesized by many aromatic plants. Anethole is a substance that humans can safely consume and has been studied for years as a biologically active molecule to treat a variety of conditions, including nerve damage, gastritis, inflammation, and nociception. [...] Read more.
Anethole is a phenolic compound synthesized by many aromatic plants. Anethole is a substance that humans can safely consume and has been studied for years as a biologically active molecule to treat a variety of conditions, including nerve damage, gastritis, inflammation, and nociception. Anethole is thought to carry out its biological activities through direct interaction with ion channels. Anethole is beneficial for neurodegenerative Alzheimer’s and Parkinson’s diseases. Nevertheless, nothing has been investigated regarding the effects of anethole on voltage-gated Na+ channels (VGSCs), which are major players in neuronal function. We used cultured dorsal root ganglion neurons from neonatal rats as a source of natively expressed VGSCs for electrophysiological studies using the whole-cell patch-clamp technique. Our data show that anethole interacts directly with VGSCs. Anethole quickly blocks and unblocks (when removed) voltage-activated Na+ currents in this preparation in a fully reversible manner. Anethole’s binding affinity to these channels increases when the inactive states of these channels are populated, similar to lidocaine’s effect on the same channels. Our data show that anethole inhibits neuronal activity by blocking VGSCs in a state-dependent manner. These findings relate to the putative anesthetic activity attributable to anethole, in addition to its potential benefit in neurodegenerative diseases. Full article
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10 pages, 2006 KiB  
Article
κO-SrVIA Conopeptide, a Novel Inhibitor Peptide for Two Members of the Human EAG Potassium Channel Family
by Luis Martínez-Hernández, Estuardo López-Vera, Manuel B. Aguilar, Ximena C. Rodriguez-Ruiz and Mónica A. Ortíz-Arellano
Int. J. Mol. Sci. 2023, 24(14), 11513; https://doi.org/10.3390/ijms241411513 - 15 Jul 2023
Cited by 2 | Viewed by 921
Abstract
The first conotoxin affecting the voltage-gated potassium channels of the EAG family was identified and characterized from the venom of the vermivorous species Conus spurius from the Gulf of Mexico. This conopeptide, initially named Cs68 and later designated κO-SrVIA, is extremely hydrophobic and [...] Read more.
The first conotoxin affecting the voltage-gated potassium channels of the EAG family was identified and characterized from the venom of the vermivorous species Conus spurius from the Gulf of Mexico. This conopeptide, initially named Cs68 and later designated κO-SrVIA, is extremely hydrophobic and comprises 31 amino acid residues, including six Cysteines in the framework VI/VII, and a free C-terminus. It inhibits the currents mediated by two human EAG subtypes, Kv10.1 (IC50 = 1.88 ± 1.08 µM) and Kv11.1 (IC50 = 2.44 ± 1.06 µM), and also the human subtype Kv1.6 (IC50 = 3.6 ± 1.04 µM). Despite its clear effects on potassium channels, it shares a high sequence identity with δ-like-AtVIA and δ-TsVIA. Also, κO-SrVIA is the third conopeptide from the venom of C. spurius with effects on potassium channels, and the seventh conotoxin that blocks Kv1.6 channels. Full article
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