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Special Issue "Purine and Its Derivatives"

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

Deadline for manuscript submissions: closed (20 September 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Ramachandra S. Hosmane

Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA
Website | E-Mail
Interests: heterocycles; nucleosides; nucleotides; medicinal chemistry; organic synthesis; purines; pyrimidines; enzymes of purine and pyrimidine metabolism; bioorganic synthesis

Special Issue Information

Dear Colleagues,

The purine ring system (imidazo[4,5-d]pyrimidine) is among the most ubiquitous of all the heterocyclic compounds. Although purine itself has never been found in nature, substituted purines like adenine and guanine or their respective nucleoside/nucleotide derivatives are the most common class of nitrogen heterocycles which play crucial roles in a wide variety of functions of living species. As nucleotides (AMP, GMP), they are the building blocks of nucleic acids (RNA/DNA). They serve as energy cofactors (ATP, GTP), as part of coenzymes (NAD/FAD) in oxidation-reduction reactions, as important second messengers in many intracellular signal transduction processes (cAMP/cGMP, or as direct neurotransmitters by binding to purinergic receptors (adenosine receptors). Therefore, it is not surprising that the analogues of purines have found utility both as chemotherapeutics (antiviral, antibiotic, and anticancer agents) and pharmacodynamic entities (regulation of myocardial oxygen consumption and cardiac blood flow). They can also act as substrates or inhibitors of enzymes of purine metabolism (ADA, Guanase, HGPRTase, PNPase, etc) in order to exert their chemotherapeutic property. In addition, their ability to act as agonists or antagonists of A1/A2A receptors is the basis for modulation of pharmacodynamic property. Finally, they can be excellent probes for elucidation of biochemical mechanisms (e.g. fluorescent -adenosine) and biophysical characteristics of nucleic acids (e.g. 8-bromoguanosine).
The availability of new methods for metal-mediated coupling with aryl or heteroaryl halide substrates has expanded the range of synthetically accessible aryl-purine derivatives. For example, aryl boronic acids are now readily available reagents for metal-mediated C-C and C-N coupling reactions. The palladium and nickel catalysts catalyze the coupling reactions that result in C-C bond formation at positions C2, C6 and C8 of purines. The reactivity at C6 position has been successfully demonstrated using fluoro-, chloro-, bromo-, iodo-, sulfanyl, sulfonyloxy- and azole-substrates. Copper-mediated N-arylations are known to occur at positions N7 and N9. These methods are also applicable using solid-supported purine substrates and provide convenient access to structurally diverse purine derivatives with applications in drug discovery. 
Since the topic on “Purines and Its Derivatives” is obviously too vast and broad to cover it all in a single issue, and considering that this special issue is released as part of the journal “Pharmaceuticals”, we will mainly focus on medicinal and pharmaceutical aspects of purines that are deemed most important based on the recent literature published during the last 5 years or so. The following are only some of the representative topics, and in no way meant to be a comprehensive list. Any subject that deals with medicinal and pharmaceutical aspects of purines in the broadest sense will be given due consideration for inclusion.

(1) Role of purines in the regulation of metabolic networks and signal transduction: 
(2) Use of uric Acid and its derivatives in the treatment of multiple sclerosis (MS) and Parkinson’s disease (PD 
(3) Use of fludarabine and its analogs in the treatment of chronic lymphocytic leukemia (CLL)
(4) The role of purine-based cyclin-dependent kinase (CDK) inhibitors in promoting apoptosis of cancer cells
(5) C-8 Aryl purines and their nucleoside/nucleotide derivatives
(6) Purinome as the target for drug discovery 
(7) Use of cyclonucleosides in the treatment of viruses and cancer
(8)Synthesis and use of 8-Azapurines with antiviral and anticancer properties: 
(9) Synthesis and use of thiopurines in the treatment of leukemia 
(10) Targeting purine salvage pathway for development of antimalarials

Prof. Dr. Ramachandra S. Hosmane
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 quarterly 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 800 CHF (Swiss Francs).

Published Papers (3 papers)

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Research

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Open AccessCommunication An Allosteric Modulator of the Adenosine A1 Receptor Improves Cardiac Function Following Ischaemia in Murine Isolated Hearts
Pharmaceuticals 2013, 6(4), 546-556; doi:10.3390/ph6040546
Received: 4 March 2013 / Revised: 26 March 2013 / Accepted: 1 April 2013 / Published: 12 April 2013
Cited by 5 | PDF Full-text (517 KB) | HTML Full-text | XML Full-text
Abstract
The effect of an allosteric modulator of the adenosine A1 receptors was investigated using an ischaemia-reperfusion protocol in murine isolated hearts. Isolated hearts were perfused with Kreb-Henseleit solution gassed with carbogen gas (95% O2 and 5% CO2) in Langendorff
[...] Read more.
The effect of an allosteric modulator of the adenosine A1 receptors was investigated using an ischaemia-reperfusion protocol in murine isolated hearts. Isolated hearts were perfused with Kreb-Henseleit solution gassed with carbogen gas (95% O2 and 5% CO2) in Langendorff mode and electrically paced at 480 bpm. Following 20 min equilibration and 20 min global normothermic ischaemia, the allosteric modulator VCP333 (1 μM) or the adenosine A1 receptor partial agonist VCP102 (10 μM) were infused after 5 min of reperfusion for 15 min. Upon termination of the drug treatment, reperfusion continued for a further 40 min. At the end of 60 min reperfusion, treatment with VCP333 or VCP102 improved the recovery of the left ventricular developed pressure when compared to control group responses (p < 0.05). Neither compound affected end diastolic pressure, coronary flow rates or dP/dtmax values when compared to control tissues during reperfusion (p > 0.05). The infusion of VCP102 or VCP333 during reperfusion reduced cardiac troponin I efflux to 6.7% and 25% respectively of control heart efflux (p < 0.05). This data indicates that the allosteric modulator of the adenosine A1 receptor (VCP333) has similar characteristics to the adenosine receptor partial agonist VCP102 as it improves cardiac function and reduces myocardial cell death following an ischaemic episode. Full article
(This article belongs to the Special Issue Purine and Its Derivatives)

Review

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Open AccessReview Metabolic Interactions of Purine Derivatives with Human ABC Transporter ABCG2: Genetic Testing to Assess Gout Risk
Pharmaceuticals 2013, 6(11), 1347-1360; doi:10.3390/ph6111347
Received: 30 September 2013 / Revised: 22 October 2013 / Accepted: 27 October 2013 / Published: 4 November 2013
Cited by 5 | PDF Full-text (317 KB) | HTML Full-text | XML Full-text
Abstract
In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through
[...] Read more.
In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. Uric acid is the end product of purine metabolism in humans. Two-thirds of uric acid in the human body is normally excreted through the kidney, whereas one-third undergoes uricolysis (decomposition of uric acid) in the gut. Elevated serum uric acid levels result in gout and could be a risk factor for cardiovascular disease and diabetes. Recent studies have shown that human ATP-binding cassette transporter ABCG2 plays a role of renal excretion of uric acid. Two non-synonymous single nucleotide polymorphisms (SNPs), i.e., 421C>A (major) and 376C>T (minor), in the ABCG2 gene result in impaired transport activity, owing to ubiquitination-mediated proteosomal degradation and truncation of ABCG2, respectively. These genetic polymorphisms are associated with hyperuricemia and gout. Allele frequencies of those SNPs are significantly higher in Asian populations than they are in African and Caucasian populations. A rapid and isothermal genotyping method has been developed to detect the SNP 421C>A, where one drop of peripheral blood is sufficient for the detection. Development of simple genotyping methods would serve to improve prevention and early therapeutic intervention for high-risk individuals in personalized healthcare. Full article
(This article belongs to the Special Issue Purine and Its Derivatives)
Figures

Open AccessReview Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds through the Inhibition of Purinergic P2X Receptors
Pharmaceuticals 2013, 6(5), 650-658; doi:10.3390/ph6050650
Received: 4 March 2013 / Revised: 18 April 2013 / Accepted: 22 April 2013 / Published: 29 April 2013
Cited by 9 | PDF Full-text (136 KB) | HTML Full-text | XML Full-text
Abstract
Natural products have reemerged in traditional medicine as a potential source of new molecules or phytomedicines to help with health disorders. It has been established that members of the P2X subfamily, ATP-gated ion channels, are crucial to the inflammatory process and pain signalization.
[...] Read more.
Natural products have reemerged in traditional medicine as a potential source of new molecules or phytomedicines to help with health disorders. It has been established that members of the P2X subfamily, ATP-gated ion channels, are crucial to the inflammatory process and pain signalization. As such, several preclinical studies have demonstrated that P2X2R, P2X3R, P2X4R and P2X7R are promising pharmacological targets to control inflammatory and pain disorders. Several studies have indicated that natural products could be a good source of the new specific molecules needed for the treatment of diseases linked to inflammation and pain disorders through the regulation of these receptors. Herein, we discuss and give an overview of the applicability of natural products as a source to obtain P2X receptors (P2XR) selective antagonists for use in clinical treatment, which require further investigation. Full article
(This article belongs to the Special Issue Purine and Its Derivatives)

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