Special Issue "Adenosine Receptors as Attractive Targets in Human Diseases"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: 30 June 2020.

Special Issue Editors

Prof. Vittoria Colotta
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Guest Editor
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Italy
Interests: medicinal chemistry; drug design; small molecules; heterocyclic compounds; adenosine receptor ligands; glutamate receptor antagonists; protein kinase CK2 inhibitors; carbonic anhydrase inhibitors
Prof. Daniela Catarzi
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Guest Editor
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff, 6, 50019 Sesto Fiorentino, Italy
Interests: medicinal chemistry; rational drug design; heterocyclic compounds; structure–activity relationships; adenosine receptor ligands; glutamate receptor antagonists; carbonic anhydrase inhibitors; protein kinase CK2 inhibitors
Dr. Flavia Varano
Website
Guest Editor
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff, 6, 50019 Sesto Fiorentino, Italy
Interests: drug design; heterocyclic compounds; adenosine receptors antagonists; glutamate receptor antagonists; protein kinase CK2 inhibitors; carbonic anhydrase inhibitors

Special Issue Information

Dear Colleagues,

Adenosine is a ubiquitous neuromodulator, both in the central and peripheral nervous systems, and is also present in almost all organs and tissues. It activates G-protein coupled receptors, classified as A1, A2A, A2B and A3 adenosine receptor (AR) subtypes, which have different tissue/organ distribution and effector couplings. Thus, adenosine modulates a wide variety of physiological processes, such as neuronal and cardiovascular activities, immune system functions and cellular metabolism, and it is also implicated in different pathological conditions. Although AR roles are still far from being completely understood, targeting ARs has been proven to be a valid mean for therapeutic and diagnostic intervention in several diseases, thus prompting scientists to search for new molecules able to modulate, directly or indirectly, AR functions. This Special Issue is aimed at providing the reader with recent advances in the field of ARs as target in human diseases.

Authors are invited to submit original articles dealing with their research in this area of investigation. The proposed topics include, but are not limited to, new AR ligands, AR allosteric modulators or enzyme modulators, designed as chemical probe for the study of adenosine pharmacological role and to highlight the AR-mediated therapeutic effects. Review articles summarizing the current knowledge on adenosine receptors and their ligands will be also of interest.

Prof. Vittoria Colotta
Prof. Daniela Catarzi
Dr. Flavia Varano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • G protein-coupled receptors
  • adenosine receptors
  • adenosine receptor ligands
  • allosteric modulators
  • rational design
  • multitarget-directed drugs
  • computational studies
  • molecular docking
  • therapeutics

Published Papers (3 papers)

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Open AccessArticle
Amino-3,5-Dicyanopyridines Targeting the Adenosine Receptors. Ranging from Pan Ligands to Combined A1/A2B Partial Agonists
Pharmaceuticals 2019, 12(4), 159; https://doi.org/10.3390/ph12040159 - 22 Oct 2019
Abstract
The amino-3,5-dicyanopyridine derivatives belong to an intriguing series of adenosine receptor (AR) ligands that has been developed by both academic researchers and industry. Indeed, the studies carried out to date underline the versatility of the dicyanopyridine scaffold to obtain AR ligands with not [...] Read more.
The amino-3,5-dicyanopyridine derivatives belong to an intriguing series of adenosine receptor (AR) ligands that has been developed by both academic researchers and industry. Indeed, the studies carried out to date underline the versatility of the dicyanopyridine scaffold to obtain AR ligands with not only a wide range of affinities but also with diverse degrees of efficacies at the different ARs. These observations prompted us to investigate on the structure–activity relationships (SARs) of this series leading to important previously reported results. The present SAR study has helped to confirm the 1H-imidazol-2-yl group at R2 position as an important feature for producing potent AR agonists. Moreover, the nature of the R1 substituent highly affects not only affinity/activity at the hA1 and hA2B ARs but also selectivity versus the other subtypes. Potent hA1 and hA2B AR ligands were developed, and among them, the 2-amino-6-[(1H-imidazol-2-ylmethyl)sulfanyl]-4-[4-(prop-2-en-1-yloxy)phenyl]pyridine-3,5-dicarbonitrile (3) is active in the low nanomolar range at these subtypes and shows a good trend of selectivity versus both the hA2A and hA3 ARs. This combined hA1/hA2B partial agonist activity leads to a synergistic effect on glucose homeostasis and could potentially be beneficial in treating diabetes and related complications. Full article
(This article belongs to the Special Issue Adenosine Receptors as Attractive Targets in Human Diseases)
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Review

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Open AccessReview
Chemical Probes for the Adenosine Receptors
Pharmaceuticals 2019, 12(4), 168; https://doi.org/10.3390/ph12040168 - 12 Nov 2019
Cited by 1
Abstract
Research on the adenosine receptors has been supported by the continuous discovery of new chemical probes characterized by more and more affinity and selectivity for the single adenosine receptor subtypes (A1, A2A, A2B and A3 adenosine receptors). [...] Read more.
Research on the adenosine receptors has been supported by the continuous discovery of new chemical probes characterized by more and more affinity and selectivity for the single adenosine receptor subtypes (A1, A2A, A2B and A3 adenosine receptors). Furthermore, the development of new techniques for the detection of G protein-coupled receptors (GPCR) requires new specific probes. In fact, if in the past radioligands were the most important GPCR probes for detection, compound screening and diagnostic purposes, nowadays, increasing importance is given to fluorescent and covalent ligands. In fact, advances in techniques such as fluorescence resonance energy transfer (FRET) and fluorescent polarization, as well as new applications in flow cytometry and different fluorescence-based microscopic techniques, are at the origin of the extensive research of new fluorescent ligands for these receptors. The resurgence of covalent ligands is due in part to a change in the common thinking in the medicinal chemistry community that a covalent drug is necessarily more toxic than a reversible one, and in part to the useful application of covalent ligands in GPCR structural biology. In this review, an updated collection of available chemical probes targeting adenosine receptors is reported. Full article
(This article belongs to the Special Issue Adenosine Receptors as Attractive Targets in Human Diseases)
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Open AccessFeature PaperReview
Non-Nucleoside Agonists of the Adenosine Receptors: An Overview
Pharmaceuticals 2019, 12(4), 150; https://doi.org/10.3390/ph12040150 - 08 Oct 2019
Cited by 1
Abstract
Potent and selective adenosine receptor (AR) agonists are of pharmacological interest for the treatment of a wide range of diseases and conditions. Among these derivatives, nucleoside-based agonists represent the great majority of molecules developed and reported to date. However, the limited availability of [...] Read more.
Potent and selective adenosine receptor (AR) agonists are of pharmacological interest for the treatment of a wide range of diseases and conditions. Among these derivatives, nucleoside-based agonists represent the great majority of molecules developed and reported to date. However, the limited availability of compounds selective for a specific AR subtype (i.e., A2BAR) and a generally long and complex synthetic route for largely substituted nucleosides are the main drawbacks of this category of molecules. Non-nucleoside agonists represent an alternative set of compounds able to stimulate the AR function and based on simplified structures. This review provides an updated overview on the structural classes of non-nucleoside AR agonists and their biological activities, with emphasis on the main derivatives reported in the literature. A focus is also given to the synthetic routes employed to develop these derivatives and on molecular modeling studies simulating their interaction with ARs. Full article
(This article belongs to the Special Issue Adenosine Receptors as Attractive Targets in Human Diseases)
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