Journal articles: 'Antiviral nucleosides'

1

Storer, Richard, and Tarek S. Mansour. "Antiviral Nucleosides." Current Pharmaceutical Design 3, no. 2 (April 1997): 227–64. http://dx.doi.org/10.2174/138161280302221006121841.

Full text

Abstract:

Abstract: This article provides an overview of the field of nucleoside antiviral agents in so far as they have some level of current interest. It considers compounds in a number of structural classes: conventional nucleoside analogues, acyclics, carbocyclics, thio, heterosubstituted and those having "unnatural" L stereochemistry. In addition, it deals with important derivative subclasses such as phosphonate mimics of nucleotides. We indicate the current•status of leading compounds, which in many cases is clinical evaluation, and position with regard to licensing, and reflect the current level and style of activities within each particular class. Our other major objective has been to incorporate a review of the major publications appearing in the last two years in the area of antiviral nucleosides. This includes both biological and clinical studies as well as the more significant advances in synthetic approaches to compounds in all classes. We refer extensively throughout to other relevant review articles which have covered particular areas -of investigation or have dealt in depth with a single compound.

APA, Harvard, Vancouver, ISO, and other styles

2

Choo, Hyunah, James R. Beadle, Earl R. Kern, Mark N. Prichard, Kathy A. Keith, Caroll B. Hartline, Julissa Trahan, Kathy A. Aldern, Brent E. Korba, and Karl Y. Hostetler. "Antiviral Activities of Novel 5-Phosphono-Pent-2-en-1-yl Nucleosides and Their Alkoxyalkyl Phosphonoesters." Antimicrobial Agents and Chemotherapy 51, no. 2 (November 27, 2006): 611–15. http://dx.doi.org/10.1128/aac.00444-06.

Full text

Abstract:

ABSTRACT Three acyclic nucleoside phosphonates are currently approved for clinical use against infections caused by cytomegalovirus (Vistide), hepatitis B virus (Hepsera), and human immunodeficiency virus type 1 (Viread). This important antiviral class inhibits viral polymerases after cellular uptake and conversion to their diphosphates, bypassing the first phosphorylation, which is required for conventional nucleoside antivirals. Small chemical alterations in the acyclic side chain lead to marked differences in antiviral activity and the spectrum of activity of acyclic nucleoside phosphonates against various classes of viral agents. We synthesized a new class of acyclic nucleoside phosphonates based on a 5-phosphono-pent-2-en-1-yl base motif in which the oxygen heteroatom usually present in acyclic nucleoside phosphonates has been replaced with a double bond. Since the intrinsic phosphonate moiety leads to low oral bioavailability and impaired cellular penetration, we also prepared the hexadecyloxypropyl esters of the 5-phosphono-pent-2-en-1-yl nucleosides. Our earlier work showed that this markedly increases antiviral activity and oral bioavailability. Although the 5-phosphono-pent-2-en-1-yl nucleosides themselves were not active, the hexadecyloxypropyl esters were active against DNA viruses and hepatitis B virus, in vitro. Notably, the hexadecyloxypropyl ester of 9-(5-phosphono-pent-2-en-1-yl)-adenine was active against hepatitis B virus mutants resistant to lamivudine, emtricitabine, and adefovir.

APA, Harvard, Vancouver, ISO, and other styles

3

Robins, Morris J., Danuta Madej, Fritz Hansske, John S. Wilson, Gilles Gosselin, Marie-Christine Bergogne, Jean-Louis Imbach, Jan Balzarini, and Erik De Clercq. "Nucleic acid related compounds. 53. Synthesis and biological evaluation of 2′-deoxy-β-threo-pentofuranosyl nucleosides. "Reversion to starting alcohol" in Barton-type reductions of thionocarbonates." Canadian Journal of Chemistry 66, no. 5 (May 1, 1988): 1258–62. http://dx.doi.org/10.1139/v88-204.

Full text

Abstract:

Treatment of selectively 3′,5′-protected β-D-xylofuranosyl nucleosides (4) with phenyl chlorothionocarbonate and DMAP followed by hydrogenolysis of the resulting (2′-O-phenoxythiocarbonyl) phenyl thionocarbonate esters (6) with tributylstannane/AIBN, and deprotection, gave 2′-deoxy-β-D-threo-pentofuranosyl nucleosides (7). Formation of a by-product bis(nucleosid-2′-yl)thionocarbonate dimer (8) was detected in the uracil nucleoside reaction sequence. Its subsequent reduction provides one explanation for "reversion to starting alcohol" in Barton-type deoxygenation reactions. Only the guanine 2′-deoxynucleoside analogue (7b) had (weak) antiviral activity (against herpes simplex virus type 1).

APA, Harvard, Vancouver, ISO, and other styles

4

Komiotis, Dimitri, Stella Manta, Evangelia Tsoukala, and Niki Tzioumaki. "Antiviral Unsaturated Nucleosides." Anti-Infective Agents in Medicinal Chemistry 7, no. 4 (October 1, 2008): 219–44. http://dx.doi.org/10.2174/187152108785908848.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Shi, Junxing, Judy S. Mathew, Phillip M. Tharnish, Suguna Rachakonda, S. Balakrishna Pai, Marjorie Adams, Jason P. Grier, et al. "N4-Acyl-Modified D-2′,3′-Dideoxy-5-Fluorocytidine Nucleoside Analogues with Improved Antiviral Activity." Antiviral Chemistry and Chemotherapy 14, no. 2 (April 2003): 81–90. http://dx.doi.org/10.1177/095632020301400203.

Full text

Abstract:

A series of 2,3-dideoxy (D2) and 2,3-didehydro-2,3-dideoxy (D4) 5-fluorocytosine nucleosides modified with substituted benzoyl, heteroaromatic carbonyl, cycloalkylcarbonyl and alkanoyl at the N4-position were synthesized and evaluated for anti-human immunodeficiency virus type 1 (HIV-1) and anti-hepatitis B virus (HBV) activity in vitro. For most D2-nucleosides, N4-substitutions improved the anti-HIV-1 activity markedly without increasing the cytotoxicity. In the D4-nucleosides series, some of the substituents at the N4-position enhanced the anti-HIV-1 activity with a modest increase in the cytotoxicity. The most potent and selective N4-modified nucleoside for the D2-series was N4- p-iodobenzoyl-D2FC, which had a 46-fold increase in anti-HIV-1 potency in MT-2 cells compared to the parent nucleoside D-D2FC. In the D4-series, N4- p-bromobenzoyl-D4FC was 12-fold more potent in MT-2 cells compared to the parent nucleoside D-D4FC. All eight N4- p-halobenzoyl-substituted D2- and D4-nucleosides evaluated against HBV in HepAD38 cells demonstrated equal or greater potency than the two parental compounds, D-D2FC and D-D4FC. The N4-modification especially in the D2-nucleoside series containing the N4-nicotinoyl, o-nitrobenzoyl and n-butyryl showed a significant reduction in mitochondrial toxicity relative to the parent nucleoside analogue. Although the 5′-triphosphate of the parent compound (D-D4FC-TP) was formed from the N4-acyl-D4FC analogues in different cells, the levels of the 5′-triphosphate nucleotide did not correlate with the cell-derived 90% effective antiviral concentrations (EC90), suggesting that a direct interaction of the triphosphates of these N4-acyl nucleosides was involved in the antiviral activity.

APA, Harvard, Vancouver, ISO, and other styles

6

Wiebe, Leonard, Edward Knaus, A. Majid Cheraghali, Rakesh Kumar, Kevin Morin, and L. Wang. "5-Halo-6-alkoxy-5,6-dihydro-pyrimidine Nucleosides: Antiviral Nucleosides or Nucleoside Prodrugs?" Nucleosides, Nucleotides and Nucleic Acids 14, no. 3 (May 1, 1995): 501–5. http://dx.doi.org/10.1080/15257779508012413.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

MANSOUR, T. S., and R. STORER. "ChemInform Abstract: Antiviral Nucleosides." ChemInform 28, no. 48 (August 2, 2010): no. http://dx.doi.org/10.1002/chin.199748326.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Bassetto, Marcella, Cecilia M. Cima, Mattia Basso, Martina Salerno, Frank Schwarze, Daniela Friese, Joachim J. Bugert, and Andrea Brancale. "Novel Nucleoside Analogues as Effective Antiviral Agents for Zika Virus Infections." Molecules 25, no. 20 (October 20, 2020): 4813. http://dx.doi.org/10.3390/molecules25204813.

Full text

Abstract:

Previously considered a neglected flavivirus, Zika virus has recently emerged as a public health concern due to its ability to spread rapidly and cause severe neurological disorders, such as microcephaly in newborn babies from infected mothers, and Guillain-Barré syndrome in adults. Despite extensive efforts towards the identification of effective therapies, specific antivirals are still not available. As part of ongoing medicinal chemistry studies to identify new antiviral agents, we screened against Zika virus replication in vitro in a targeted internal library of small-molecule agents, comprising both nucleoside and non-nucleoside agents. Among the compounds evaluated, novel aryloxyphosphoramidate prodrugs of the nucleosides 2′-C-methyl-adenosine, 2-CMA, and 7-deaza-2′C-methyl-adenosine, 7-DMA, were found to significantly inhibit the virus-induced cytopathic effect in multiple relevant cell lines. In addition, one of these prodrugs exhibits a synergistic antiviral effect against Zika virus when applied in combination with an indirect antiviral agent, a l-dideoxy bicyclic pyrimidine nucleoside analogue, which potently inhibits vaccinia and measles viruses in vitro by targeting a host pathway. Our findings provide a solid basis for further development of an antiviral therapy for Zika virus infections, possibly exploiting a dual approach combining two different agents, one targeting the viral polymerase (direct-acting antiviral), the second targeting a host-directed autophagy mechanism.

APA, Harvard, Vancouver, ISO, and other styles

9

Erickson-Viitanen, Susan, Jing-Tao Wu, Guoen Shi, Steven Unger, Robert W. King, Barbara Fish, Ronald Klabe, et al. "Cellular Pharmacology of D-d4FC, a Nucleoside Analogue Active against Drug-Resistant HIV." Antiviral Chemistry and Chemotherapy 14, no. 1 (February 2003): 39–47. http://dx.doi.org/10.1177/095632020301400104.

Full text

Abstract:

The backbone of effective highly active antiretroviral therapy regimens for the treatment of HIV infections currently contains at least two nucleosides. Among the features that influence the potency of each component of a regimen and the overall efficacy of the combination are the cellular uptake and bioconversion of nucleoside analogues to their active triphosphate form, and the extent of possible interactions in these steps that might occur when more than one nucleoside is used in a regimen. D-d4FC (Reverset™), a new cytidine analogue with the ability to inhibit many nucleoside-resistant viral variants, was examined for these parameters. In phytohemaglutinin-stimulated human peripheral blood mononuclear cells, D-d4FC was taken up in a rapid (8 h to 50% maximal value), saturable (plateau above 10 μM parent nucleoside concentration) process, resulting in levels of D-d4FC triphosphate that should provide potent antiviral activity against a variety of virus genotypes. Based on measurement of antiviral effects in cell culture, additive and in some cases, synergistic interactions were observed with protease inhibitors, non-nucleoside reverse transcriptase inhibitors or other nucleosides, including cytidine analogues.

APA, Harvard, Vancouver, ISO, and other styles

10

Lee, Kyeong, and Chung K. Chu. "Molecular Modeling Approach to Understanding the Mode of Action of l-Nucleosides as Antiviral Agents." Antimicrobial Agents and Chemotherapy 45, no. 1 (January 1, 2001): 138–44. http://dx.doi.org/10.1128/aac.45.1.138-144.2001.

Full text

Abstract:

ABSTRACT A series of unnatural l-nucleosides such as 3TC, FTC and l-FMAU have been found to be potent antiviral agents. The mode of action of l-nucleosides has been found to be similar to that of d-nucleosides as antiviral agents, despite their unnatural stereochemistry, that is, nucleotide formation by kinases followed by interaction with the reverse transcriptase (RT) of HIV or DNA polymerase. To date, the mode of action of nucleoside inhibitors at the molecular level with respect to the active conformations of the 5′-triphosphates as well as the interaction with the RT is not known. Recently, the X-ray crystal structure of the RT-DNA-dTTP catalytic complex has been reported. Computer modeling has been performed for several pairs ofd- and l-nucleoside inhibitors using the HIV-1 RT model and crystal coordinate data from a subset of the protein surrounding the deoxynucleoside triphosphate (dNTP) binding pocket region. Results from our modeling studies ofd-/l-zidovudine,d-/l-3TC,d-/l-dideoxycytosine triphosphates, dTTP and dCTP show that their binding energies correlate with the reported 50% effective concentrations. Modeling results are also discussed with respect to favorable conformations of each inhibitor at the dNTP site in the polymerization process. Additionally, the clinically important M184V mutation, which confers resistance against 3TC and FTC, was studied with our modeling system. The binding energy patterns of nucleoside inhibitors at the M184V mutation site correlate with the reported antiviral data.

APA, Harvard, Vancouver, ISO, and other styles

11

Seley-Radtke, Katherine. "Flexibility—Not just for yoga anymore!" Antiviral Chemistry and Chemotherapy 26 (January 2018): 204020661875678. http://dx.doi.org/10.1177/2040206618756788.

Full text

Abstract:

Over the past few years, nucleosides have maintained a prominent role as one of the cornerstones of antiviral and anticancer therapeutics, and many approaches to nucleoside drug design have been pursued. One such approach involves flexibility in the sugar moiety of nucleosides, for example, in the highly successful anti-HIV and HBV drug tenofovir. In contrast, introduction of flexibility to the nucleobase scaffold has only more recently gained significance with the invention of our fleximers. The history, development, and some biological relevance for this innovative class of nucleosides are detailed herein.

APA, Harvard, Vancouver, ISO, and other styles

12

Soto-Acosta, Ruben, Tiffany C. Edwards, Christine D. Dreis, Venkatramana D. Krishna, Maxim C.-J. Cheeran, Li Qiu, Jiashu Xie, Laurent F. Bonnac, and Robert J. Geraghty. "Enhancing the Antiviral Potency of Nucleobases for Potential Broad-Spectrum Antiviral Therapies." Viruses 13, no. 12 (December 14, 2021): 2508. http://dx.doi.org/10.3390/v13122508.

Full text

Abstract:

Broad-spectrum antiviral therapies hold promise as a first-line defense against emerging viruses by blunting illness severity and spread until vaccines and virus-specific antivirals are developed. The nucleobase favipiravir, often discussed as a broad-spectrum inhibitor, was not effective in recent clinical trials involving patients infected with Ebola virus or SARS-CoV-2. A drawback of favipiravir use is its rapid clearance before conversion to its active nucleoside-5′-triphosphate form. In this work, we report a synergistic reduction of flavivirus (dengue, Zika), orthomyxovirus (influenza A), and coronavirus (HCoV-OC43 and SARS-CoV-2) replication when the nucleobases favipiravir or T-1105 were combined with the antimetabolite 6-methylmercaptopurine riboside (6MMPr). The 6MMPr/T-1105 combination increased the C-U and G-A mutation frequency compared to treatment with T-1105 or 6MMPr alone. A further analysis revealed that the 6MMPr/T-1105 co-treatment reduced cellular purine nucleotide triphosphate synthesis and increased conversion of the antiviral nucleobase to its nucleoside-5′-monophosphate, -diphosphate, and -triphosphate forms. The 6MMPr co-treatment specifically increased production of the active antiviral form of the nucleobases (but not corresponding nucleosides) while also reducing levels of competing cellular NTPs to produce the synergistic effect. This in-depth work establishes a foundation for development of small molecules as possible co-treatments with nucleobases like favipiravir in response to emerging RNA virus infections.

APA, Harvard, Vancouver, ISO, and other styles

13

Young, James D. "The SLC28 (CNT) and SLC29 (ENT) nucleoside transporter families: a 30-year collaborative odyssey." Biochemical Society Transactions 44, no. 3 (June 9, 2016): 869–76. http://dx.doi.org/10.1042/bst20160038.

Full text

Abstract:

Specialized nucleoside transporter (NT) proteins are required for passage of nucleosides and hydrophilic nucleoside analogues across biological membranes. Physiologic nucleosides serve as central salvage metabolites in nucleotide biosynthesis, and nucleoside analogues are used as chemotherapeutic agents in the treatment of cancer and antiviral diseases. The nucleoside adenosine modulates numerous cellular events via purino-receptor cell signalling pathways. Human NTs are divided into two structurally unrelated protein families: the SLC28 concentrative nucleoside transporter (CNT) family and the SLC29 equilibrative nucleoside transporter (ENT) family. Human CNTs are inwardly directed Na+-dependent nucleoside transporters found predominantly in intestinal and renal epithelial and other specialized cell types. Human ENTs mediate bidirectional fluxes of purine and pyrimidine nucleosides down their concentration gradients and are ubiquitously found in most, possibly all, cell types. Both protein families are evolutionarily old: CNTs are present in both eukaryotes and prokaryotes; ENTs are widely distributed in mammalian, lower vertebrate and other eukaryote species. This mini-review describes a 30-year collaboration with Professor Stephen Baldwin to identify and understand the structures and functions of these physiologically and clinically important transport proteins.

APA, Harvard, Vancouver, ISO, and other styles

14

van Roey, P., W. A. Pangborn, R. F. Schinazi, G. Painter, and D. C. Liotta. "Absolute Configuration of the Antiviral Agent (−)-cis-5-Fluoro-1-[2-Hydroxymethyl)-1,3-Oxathiolan-5-yl]Cytosine." Antiviral Chemistry and Chemotherapy 4, no. 6 (December 1993): 369–75. http://dx.doi.org/10.1177/095632029300400609.

Full text

Abstract:

The structure and absolute configuration of (−)- cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FTC), has been determined by X-ray crystallographic analysis. The results confirm that the L-isomer of the nucleoside analogue is the most active enantiomer and that the correct absolute configuration of (−)-FTC is 5-fluoro-(2′R,5′S)-(−)-1-[2-hydroxymethyl)oxathiolan-5-yl]-fluorocytosine. The two molecules in the asymmetric unit show conformations that combine conformational features of two other classes of potent antiviral nucleosides. Both oxathiolane rings have the 3′-sulphur atom in nearly perfect S3′- exo envelope conformations, similar to what is observed for 3′-azido-3′-deoxythymidine (AZT) and 2′,3′-dideoxycytidine. One of the two molecules has a glycosylic link conformation in which the base is eclipsed with the C5′-O1′ bond. This mimics the high- anti conformation that has been observed in the structures of several 2′,3′-didehydro-2′,3′-dideoxypyrimidine nucleosides but is inaccessible for saturated pyrimidine nucleosides. However, the observed conformations cannot be superimposed adequately with other active antiviral nucleosides to suggest a common ‘active site’ conformation.

APA, Harvard, Vancouver, ISO, and other styles

15

Cabrita, Miguel A., Stephen A. Baldwin, James D. Young, and Carol E. Cass. "Molecular biology and regulation of nucleoside and nucleobase transporter proteins in eukaryotes and prokaryotes." Biochemistry and Cell Biology 80, no. 5 (October 1, 2002): 623–38. http://dx.doi.org/10.1139/o02-153.

Full text

Abstract:

The molecular cloning of cDNAs encoding nucleoside transporter proteins has greatly advanced understanding of how nucleoside permeants are translocated across cell membranes. The nucleoside transporter proteins identified thus far have been categorized into five distinct superfamilies. Two of these superfamilies, the equilibrative and concentrative nucleoside transporters, have human members and these will be examined in depth in this review. The human equilibrative nucleoside transporters translocate nucleosides and nucleobases bidirectionally down their concentration gradients and are important in the uptake of anticancer and antiviral nucleoside drugs. The human concentrative nucleoside transporters cotranslocate nucleosides and sodium unidirectionally against the nucleoside concentration gradients and play a vital role in certain tissues. The regulation of nucleoside and nucleobase transporters is being studied more intensely now that more tools are available. This review provides an overview of recent advances in the molecular biology and regulation of the nucleoside and nucleobase transporters.Key words: nucleoside transporter, nucleoside transport, nucleobase transporter, nucleobase transport, regulation of nucleoside and nucleobase transport, nucleoside drugs.

APA, Harvard, Vancouver, ISO, and other styles

16

Freeman, Sally, and John M. Gardiner. "Acyclic nucleosides as antiviral compounds." Molecular Biotechnology 5, no. 2 (April 1996): 125–37. http://dx.doi.org/10.1007/bf02789061.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Izawa, Kunisuke, and H. Shiragami. "Practical syntheses of antiviral nucleosides." Pure and Applied Chemistry 70, no. 2 (February 28, 1998): 313–18. http://dx.doi.org/10.1351/pac199870020313.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Podgorska, Marzena, Katarzyna Kocbuch, and Tadeusz Pawelczyk. "Recent advances in studies on biochemical and structural properties of equilibrative and concentrative nucleoside transporters." Acta Biochimica Polonica 52, no. 4 (October 25, 2005): 749–58. http://dx.doi.org/10.18388/abp.2005_3386.

Full text

Abstract:

Nucleoside transporters (NT) facilitate the movement of nucleosides and nucleobases across cell membranes. NT-mediated transport is vital for the synthesis of nucleic acids in cells that lack de novo purine synthesis. Some nucleosides display biological activity and act as signalling molecules. For example, adenosine exerts a potent action on many physiological processes including vasodilatation, hormone and neurotransmitter release, platelet aggregation, and lipolysis. Therefore, carrier-mediated transport of this nucleoside plays an important role in modulating cell function, because the efficiency of the transport processes determines adenosine availability to its receptors or to metabolizing enzymes. Nucleoside transporters are also key elements in anticancer and antiviral therapy with the use of nucleoside analogues. Mammalian cells possess two major nucleoside transporter families: equilibrative (ENT) and concentrative (CNT) Na(+)-dependent ones. This review characterizes gene loci, substrate specificity, tissue distribution, membrane topology and structure of ENT and CNT proteins. Regulation of nucleoside transporters by various factors is also presented.

APA, Harvard, Vancouver, ISO, and other styles

19

YOKOZEKI, KENZO, HYDEYUKI SHIRAE, and KOJI KUBOTA. "Enzymatic Production of Antiviral Nucleosides by the Application of Nucleoside Phosphorylase." Annals of the New York Academy of Sciences 613, no. 1 Enzyme Engine (December 1990): 757–59. http://dx.doi.org/10.1111/j.1749-6632.1990.tb18259.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Casati, Silvana, Paola Rota, Pietro Allevi, Alessandra Mingione, Roberta Ottria, and Pierangela Ciuffreda. "Clarifying the Use of Benzylidene Protecting Group for D-(+)-Ribono-1,4-Lactone, an Essential Building Block in the Synthesis of C-Nucleosides." Molecules 26, no. 21 (October 26, 2021): 6447. http://dx.doi.org/10.3390/molecules26216447.

Full text

Abstract:

In the last two years, nucleosides analogues, a class of well-established bioactive compounds, have been the subject of renewed interest from the scientific community thanks to their antiviral activity. The COVID-19 global pandemic, indeed, spread light on the antiviral drug Remdesivir, an adenine C-nucleoside analogue. This new attention of the medical community on Remdesivir prompts the medicinal chemists to investigate once again C-nucleosides. One of the essential building blocks to synthetize these compounds is the D-(+)-ribono-1,4-lactone, but some mechanistic aspects linked to the use of different carbohydrate protecting groups remain unclear. Here, we present our investigations on the use of benzylidene as a ribonolactone protecting group useful in the synthesis of C-purine nucleosides analogues. A detailed 1D and 2D NMR structural study of the obtained compounds under different reaction conditions is presented. In addition, a molecular modeling study at the B3LYP/6-31G* level of theory with the SM8 solvation model for CHCl3 and DMSO to support the obtained results is used. This study allows for clarifying mechanistic aspects as the side reactions and structural rearrangements liked to the use of the benzylidene protecting group.

APA, Harvard, Vancouver, ISO, and other styles

21

Carangio, A., S. Srinivasan, C. McGuigan, G. Andrei, R. Snoeck, E. De Clercq, and J. Balzarini. "Bicyclic Nucleoside Inhibitors of Varicella-Zoster Virus: Effect of Terminal Aryl Substitution in the Side-Chain." Antiviral Chemistry and Chemotherapy 13, no. 5 (October 2002): 263–71. http://dx.doi.org/10.1177/095632020201300501.

Full text

Abstract:

We have previously reported the discovery and preliminary structure-activity relationships of a new class of inhibitors of varicella-zoster virus (VZV). These novel furanopyrimidine nucleosides bear unusual bicyclic base moieties and exhibit complete specificity for VZV. Limited in vitro cytotoxicity has been detected and the bicyclic nucleosides are now well established as a new family of potent antivirals. Our initial studies revealed an absolute requirement of a long alkyl side-chain, with an optimal chain length of C8-C10, for antiviral activity. Following further studies, we recently reported a significant enhancement of both antiviral potency and selectivity by the inclusion of a phenyl group within the alkyl side-chain of these compounds. The new lead p-alkylphenyl analogues displayed EC50 values below 1 nM versus VZV and selectivity index values >1000000. We herein report the synthesis and characterization of a further series of alkylaryl analogues bearing terminal phenyl groups with varying n-alkyl side-chain lengths. Synthesis of the target bicyclic systems involved the Pd-catalysed coupling of terminal acetylenes with 5-iodo-2′-deoxyuridine to give intermediate 5-alkynyl nucleosides which were then cyclized in the presence of copper (I) iodide. The current compounds display excellent selectivity for VZV with no detectable in vitro cytotoxicity but despite being chemically isomeric with the previous lead p-alkylphenyl analogues, the compounds reported herein exhibit only moderate antiviral activities. A possible correlation between antiviral activity and conformational freedom of the side-chain is discussed.

APA, Harvard, Vancouver, ISO, and other styles

22

Koplūnaitė, Martyna, Kamilė Butkutė, Dominykas Špelveris, Nina Urbelienė, and Rolandas Meškys. "Enzymatic Synthesis of Modified Nucleoside 5′-Monophosphates." Catalysts 12, no. 11 (November 9, 2022): 1401. http://dx.doi.org/10.3390/catal12111401.

Full text

Abstract:

There is an extensive list of applications for nucleosides, nucleotides, and their analogues that spans from substrates and inhibitors in enzymatic research to anticancer and antiviral drugs. Nucleoside phosphates are often obtained by chemical phosphorylation reactions, although enzymatic nucleoside phosphorylation is a promising green alternative. In this work two nucleoside kinases, D. melanogaster deoxynucleoside kinase and B. subtilis deoxycytidine kinase, have been employed for the phosphorylation of various canonical and modified nucleosides, and the results between the two enzymes have been compared. It was determined that both kinases are suitable candidates for enzymatic nucleoside 5′-monophosphate synthesis, as the reaction yields are often in the 40–90% range. Deoxynucleoside kinase, however, often outperforms deoxycytidine kinase and accepts a wider range of nucleoside analogues as substrates. Hence, deoxynucleoside kinase and deoxycytidine kinase were active towards 43 and 34 of 57 tested compounds, respectively. Both nucleoside kinases have been also tested for a larger-scale synthesis of nucleoside monophosphates in the presence of a GTP regeneration system using acetate kinase from E. coli.

APA, Harvard, Vancouver, ISO, and other styles

23

Agrofoglio, Luigi, and Steven Nolan. "Olefin Metathesis Route to Antiviral Nucleosides." Current Topics in Medicinal Chemistry 5, no. 15 (November 1, 2005): 1541–58. http://dx.doi.org/10.2174/156802605775009739.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Rossi, L., S. Serafini, P. Franchetti, L. Cappellacci, A. Fraternale, A. Casabianca, G. Brandi, et al. "Targeting Nucleotide Dimers Containing Antiviral Nucleosides." Current Medicinal Chemistry -Anti-Infective Agents 4, no. 1 (January 1, 2005): 37–54. http://dx.doi.org/10.2174/1568012052931214.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Cluet, F., A. Haudrechy, P. Le Ber, P. Sinaÿ, and A. Wick. "Synthesis of potentially antiviral cyclopropyl nucleosides." Synlett 1994, no. 11 (1994): 913–15. http://dx.doi.org/10.1055/s-1994-23046.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Loakes, D., D. M. Brown, N. Mahmood, J. Balzarini, and E. De Clercq. "Antiviral Activity of Bicyclic Pyrimidine Nucleosides." Antiviral Chemistry and Chemotherapy 6, no. 6 (December 1995): 371–78. http://dx.doi.org/10.1177/095632029500600604.

Full text

Abstract:

A number of pyrimidine nucleosides, which may show two hydrogen bonding modes, have been prepared and tested for antiviral activity against a series of viruses. Whilst none of the compounds described showed significant activity against human immunodeficiency virus (HIV), the bicyclic 2′-deoxynucleoside, [2], derived from the base 6H,8H-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one, was shown to inhibit herpes simplex virus type 1 (HSV-1) at similar concentrations as BVDU1 and ACV. Compounds 13, 6-(2-deoxyribofuranosyl)-6H,8H-2-methyl-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one, and 14, N4-hydroxy-5-(2-chloroethyl)-2′-deoxyuridine, were as active as ACV against varicella-zoster virus (VZV).

APA, Harvard, Vancouver, ISO, and other styles

27

Shipitsyn, Alexander V., Natalya F. Zakirova, Evgeny F. Belanov, Tatyana R. Pronyaeva, Nina V. Fedyuk, Marina K. Kukhanova, and Andrey G. Pokrovsky. "Phosphorodiamides as Prodrugs for Antiviral Nucleosides." Nucleosides, Nucleotides and Nucleic Acids 22, no. 5-8 (October 2003): 963–66. http://dx.doi.org/10.1081/ncn-120022696.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Hyun Oh, Chang, and Joon Hee Hong. "Synthesis and Antiviral Evaluation of Novel Cyclopropyl Nucleosides, Phosphonate Nucleosides and Phosphonic Acid Nucleosides." Archiv der Pharmazie 339, no. 9 (September 2006): 507–12. http://dx.doi.org/10.1002/ardp.200600031.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Coen, Natacha, Sophie Duraffour, Dimitri Topalis, Robert Snoeck, and Graciela Andrei. "Spectrum of Activity and Mechanisms of Resistance of Various Nucleoside Derivatives against Gammaherpesviruses." Antimicrobial Agents and Chemotherapy 58, no. 12 (September 29, 2014): 7312–23. http://dx.doi.org/10.1128/aac.03957-14.

Full text

Abstract:

ABSTRACTThe susceptibilities of gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and animal rhadinoviruses, to various nucleoside analogs was investigated in this work. Besides examining the antiviral activities and modes of action of antivirals currently marketed for the treatment of alpha- and/or betaherpesvirus infections (including acyclovir, ganciclovir, penciclovir, foscarnet, and brivudin), we also investigated the structure-activity relationship of various 5-substituted uridine and cytidine molecules. The antiviral efficacy of nucleoside derivatives bearing substitutions at the 5 position was decreased if the bromovinyl was replaced by chlorovinyl. 1-β-d-Arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU), a nucleoside with an arabinose configuration of the sugar ring, exhibited no inhibitory effect against rhadinoviruses but was active against EBV. On the other hand, the fluoroarabinose cytidine analog 2′-fluoro-5-iodo-aracytosine (FIAC) showed high selectivity indices against gammaherpesviruses that were comparable to those of brivudin. Additionally, we selected brivudin- and acyclovir-resistant rhadinovirusesin vitroand characterized them by phenotypic and genotypic (i.e., sequencing of the viral thymidine kinase, protein kinase, and DNA polymerase) analysis. Here, we reveal key amino acids in these enzymes that play an important role in substrate recognition. Our data on drug susceptibility profiles of the different animal gammaherpesvirus mutants highlighted cross-resistance patterns and indicated that pyrimidine nucleoside derivatives are phosphorylated by the viral thymidine kinase and purine nucleosides are preferentially activated by the gammaherpesvirus protein kinase.

APA, Harvard, Vancouver, ISO, and other styles

30

Govindarajan, Rajgopal, George P. H. Leung, Mingyan Zhou, Chung-Ming Tse, Joanne Wang, and Jashvant D. Unadkat. "Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3." American Journal of Physiology-Gastrointestinal and Liver Physiology 296, no. 4 (April 2009): G910—G922. http://dx.doi.org/10.1152/ajpgi.90672.2008.

Full text

Abstract:

human equilibrative nucleoside transporter-3 (hENT3) was recently reported as a pH-dependent, intracellular (lysosomal) transporter capable of transporting anti-human immunodeficiency virus (HIV) dideoxynucleosides (ddNs). Because most anti-HIV ddNs (e.g., zidovudine, AZT) exhibit clinical mitochondrial toxicity, we investigated whether hENT3 facilitates transport of anti-HIV ddNs into the mitochondria. Cellular fractionation and immunofluorescence microscopy studies in several human cell lines identified a substantial presence of hENT3 in the mitochondria, with additional presence at the cell surface of two placental cell lines (JAR, JEG3). Mitochondrial or cell surface hENT3 expression was confirmed in human hepatocytes and placental tissues, respectively. Unlike endogenous hENT3, yellow fluorescent protein (YFP)-tagged hENT3 was partially directed to the lysosomes. Xenopus oocytes expressing NH2-terminal-deleted hENT3 (expressed at the cell surface) showed pH-dependent interaction with several classes of nucleosides (anti-HIV ddNs, gemcitabine, fialuridine, ribavirin) that produce mitochondrial toxicity. Transport studies in hENT3 gene-silenced JAR cells showed significant reduction in mitochondrial transport of nucleosides and nucleoside drugs. Our data suggest that cellular localization of hENT3 is cell type dependent and the native transporter is substantially expressed in mitochondria and/or cell surface. hENT3-mediated mitochondrial transport may play an important role in mediating clinically observed mitochondrial toxicity of nucleoside drugs. In addition, our finding that hENT3 is a mitochondrial transporter is consistent with the recent finding that mutations in the hENT3 gene cause an autosomal recessive disorder in humans called the H syndrome.

APA, Harvard, Vancouver, ISO, and other styles

31

Griffon, Jean-François, Sue C. Shaddix, William B. Parker, Ashraf S. Al-Madhoun, Staffan Eriksson, John A. Montgomery, and John A. Secrist III. "Synthesis and Biological Evaluation of Some 4'-C-(Hydroxymethyl)-α- and -β-D-Arabinofuranosyl Pyrimidine and Adenine Nucleosides." Collection of Czechoslovak Chemical Communications 71, no. 7 (2006): 1063–87. http://dx.doi.org/10.1135/cccc20061063.

Full text

Abstract:

A series of 4'-C-(hydroxymethyl) analogs of pyrimidine and purine nucleosides have been prepared utilizing standard methodologies, and the α and β anomers were separated. These analogs are part of our continuing efforts to identify new anticancer drugs as well as to explore the substrate specificities of these analogs with the initial activating enzymes in the metabolic pathway leading to nucleoside triphosphates. Although not cytotoxic to CCRF-CEM cells (an acute lymphoblastic leukemia of T-cell origin), many of these compounds were utilized as substrates for the various human nucleoside kinases, including deoxycytidine kinase, thymidine kinase 1, and thymidine kinase 2. Because the 4'-C-(hydroxymethyl) analog of arabinofuranosyl cytosine was identified as a good substrate with deoxycytidine kinase, its metabolism in CEM cells was evaluated. These results indicated that nucleosides with this modification could be activated in human cells without cytotoxicity, which suggested that they should be examined for antiviral activity.

APA, Harvard, Vancouver, ISO, and other styles

32

Pathy, Dr Krishnasarma. "Antiviral Nucleosides-Flu Viruses-Quinolines-COVID-19." International Journal of Research Studies in Medical and Health Sciences 5, no. 8 (2020): 14–25. http://dx.doi.org/10.22259/ijrsmhs.0508002.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Gumina, Giuseppe, Youhoon Chong, Hyunah Choo, Gyu-Yong Song, and Chung Chu. "L - Nucleosides: Antiviral Activity and Molecular Mechanism." Current Topics in Medicinal Chemistry 2, no. 10 (October 1, 2002): 1065–86. http://dx.doi.org/10.2174/1568026023393138.

Full text

APA, Harvard, Vancouver, ISO, and other styles

34

Meng, Wei-Dong, and Feng-Ling Qing. "Fluorinated Nucleosides as Antiviral and Antitumor Agents." Current Topics in Medicinal Chemistry 6, no. 14 (July 1, 2006): 1499–528. http://dx.doi.org/10.2174/156802606777951082.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Siddiqui, M. Arshad, William L. Brown, Nghe Nguyen-Ba, Dilip M. Dixit, Tarek S. Mansour, Elizabeth Hooker, K. Claire Viner, and Janet M. Cameron. "Antiviral optically pure dioxolane purine nucleosides analogues." Bioorganic & Medicinal Chemistry Letters 3, no. 8 (August 1993): 1543–46. http://dx.doi.org/10.1016/s0960-894x(00)80014-1.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Herdewijn, Piet. "Structural requirements for antiviral activity in nucleosides." Drug Discovery Today 2, no. 6 (June 1997): 235–42. http://dx.doi.org/10.1016/s1359-6446(97)01047-7.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Nair, Vasu, and Michael A. Ussery. "New hypoxanthine nucleosides with RNA antiviral activity." Antiviral Research 19, no. 2 (August 1992): 173–78. http://dx.doi.org/10.1016/0166-3542(92)90076-h.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Chu, Chung K., Li Ma, Sureyya Olgen, Claire Pierra, Jinfa Du, Giuseppe Gumina, Elizabeth Gullen, Yung-Chi Cheng, and Raymond F. Schinazi. "Synthesis and Antiviral Activity of Oxaselenolane Nucleosides." Journal of Medicinal Chemistry 43, no. 21 (October 2000): 3906–12. http://dx.doi.org/10.1021/jm990113x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Cano-Soldado, Pedro, Ignacio M. Larráyoz, Míriam Molina-Arcas, F. Javier Casado, Javier Martinez-Picado, M. Pilar Lostao, and Marçal Pastor-Anglada. "Interaction of Nucleoside Inhibitors of HIV-1 Reverse Transcriptase with the Concentrative Nucleoside Transporter-1 (Slc28A1)." Antiviral Therapy 9, no. 6 (August 2004): 993–1002. http://dx.doi.org/10.1177/135965350400900617.

Full text

Abstract:

Human concentrative nucleoside transporter-1 (hCNT1) (SLC28A1) is a widely expressed, high-affinity, pyrimi-dine-preferring, nucleoside transporter implicated in the uptake of naturally occurring pyrimidine nucleosides as well as a variety of derivatives used in anticancer treatment. Its putative role in the uptake of other pyrimidine nucleoside analogues with antiviral properties has not been studied in detail to date. Here, using a hCNT1 stably transfected cell line and the two-electrode voltage-clamp technique, we have assessed the interaction of selected pyrimidine-based antiviral drugs, inhibitors of HIV-1 reverse transcriptase such as zidovudine (AZT), stavudine (d4T), lamivudine (3TC) and zalcitabine (ddC), with hCNT1. hCNT1 transports AZT and d4T with low affinity, whereas 3TC and ddC are not translocated, the latter being able to bind the transporter protein. Selectivity appears to rely mostly upon the presence of a hydroxyl group in the 3′-position of the ribose ring. Thus, hCNT1 cannot be considered a broad-selectivity pyrimidine nucleoside carrier; in fact, very slight changes in substrate structure provoke a dramatic shift in selectivity.

APA, Harvard, Vancouver, ISO, and other styles

40

Chen, X., D. R. Sauer, and S. W. Schnellert. "Recent Developments in Pyrazofurin Analogue Design." Current Medicinal Chemistry 1, no. 2 (August 1994): 105–14. http://dx.doi.org/10.2174/092986730102220214152011.

Full text

Abstract:

Abstract: Nucleosides of 5-membered heterocycles are playing a prominent role in the design of antiviral agents. Included in this group is 4- hydroxy-3-( -D-ribofuranosyl)pyrazole-5-carboxamide (pyrazofurin), which is a naturally occurring C-nucleoside that shows significant broad spectrum in vitro antiviral activity against DNA and RNA viruses. The extent of its antiviral properties is represented by its activity against pox-, picorna, toga-, myxo-, rhabdo-, arena-, and bunyaviruses with a high degree of selectivity. Even with its promising activity and broad safety margin in cell cultures, there have been reports that the toxicity of pyrazo furin may limit its usefulness as an antiviral agent. However, others have suggested that the toxicity of pyrazofurin is unlikely to be associated with the structural components that are responsible for its antiviral properties. To evaluate this suggestion for the purpose of producing non-toxic pyrazofurin-derived agents that are effective against the virus groups mentioned above, structural modifications in pyrazofurin have recently been the subject of work in this laboratory. These efforts are described.

APA, Harvard, Vancouver, ISO, and other styles

41

Kasthuri, Mahesh, Chengwei Li, Kiran Verma, Olivia Ollinger Russell, Lyndsey Dickson, Louise McCormick, Leda Bassit, Franck Amblard, and Raymond F. Schinazi. "Synthesis of 4′-Substituted-2′-Deoxy-2′-α-Fluoro Nucleoside Analogs as Potential Antiviral Agents." Molecules 25, no. 6 (March 11, 2020): 1258. http://dx.doi.org/10.3390/molecules25061258.

Full text

Abstract:

Nucleoside analogs are widely used for the treatment of viral diseases (Hepatitis B/C, herpes and human immunodeficiency virus, HIV) and various malignancies. ALS-8176, a prodrug of the 4′-chloromethyl-2′-deoxy-2′-fluoro nucleoside ALS-8112, was evaluated in hospitalized infants for the treatment of respiratory syncytial virus (RSV), but was abandoned for unclear reasons. Based on the structure of ALS-8112, a series of novel 4′-modified-2′-deoxy-2′-fluoro nucleosides were synthesized. Newly prepared compounds were evaluated against RSV, but also against a panel of RNA viruses, including Dengue, West Nile, Chikungunya, and Zika viruses. Unfortunately, none of the compounds showed marked antiviral activity against these viruses.

APA, Harvard, Vancouver, ISO, and other styles

42

Jansa, Petr, Viktor Kolman, Alexandra Kostinová, Martin Dračínský, Helena Mertlíková-Kaiserová, and Zlatko Janeba. "Efficient synthesis and biological properties of the 2′-trifluoromethyl analogues of acyclic nucleosides and acyclic nucleoside phosphonates." Collection of Czechoslovak Chemical Communications 76, no. 10 (2011): 1187–98. http://dx.doi.org/10.1135/cccc2011105.

Full text

Abstract:

Efficient and optimized procedure for the preparation of several acyclic nucleosides and acyclic nucleoside phosphonates substituted at the C-2′ position of the aliphatic part by the trifluoromethyl group is described. Trifluoromethyloxirane was found to be an excellent reagent for the introduction of the 1,1,1-trifluoropropan-2-ol moiety. Surprisingly, the next reaction of these 1,1,1-trifluoropropan-2-ols with the reagent for the introduction of the methylphosphonic residue afforded the desired phosphonates in very high yields and finally a novel simple and scalable procedure for the isolation of free phosphonic acids, after the reaction of dialkyl phosphonates with bromotrimethylsilane, was developed. Prepared compounds were evaluated for their biological properties, but none of the prepared phosphonic acids or acyclic nucleosides exhibits any antiviral, antiproliferative or anti-toxin activities.

APA, Harvard, Vancouver, ISO, and other styles

43

Shanmugasundaram, Muthian, Annamalai Senthilvelan, and Anilkumar R. Kore. "C-5 Substituted Pyrimidine Nucleotides/Nucleosides: Recent Progress in Synthesis, Functionalization, and Applications." Current Organic Chemistry 23, no. 13 (October 9, 2019): 1439–68. http://dx.doi.org/10.2174/1385272823666190809124310.

Full text

Abstract:

The chemistry of C5 substituted pyrimidine nucleotide serves as a versatile molecular biology probe for the incorporation of DNA/RNA that has been involved in various molecular biology applications such as gene expression, chromosome, and mRNA fluorescence in situ hybridization (FISH) experiment, mutation detection on arrays and microarrays, in situ RT-PCR, and PCR. In addition to C5 substituted pyrimidine nucleotide, C5 substituted pyrimidine nucleoside displays a broad spectrum of biological applications such as antibacterial, antiviral and anticancer activities. This review focusses on the recent development in the synthesis of aminoallyl pyrimidine nucleotide, aminopropargyl pyrimidine nucleotide, fluorescent probes containing C5 substituted pyrimidine nucleotide, 2′-deoxycytidine nucleoside containing vinylsulfonamide and acrylamide modification, C5 alkenyl, C5 alkynyl, and C5 aryl pyrimidine nucleosides through palladium-catalyzed reaction, pyrimidine nucleoside containing triazole moiety through Click reaction, 5-isoxazol-3-yl-pyrimidine nucleoside, C5 azide modified pyrimidine nucleoside, 2′-deoxycytidine nucleotide containing photocleavable moiety, and uridine nucleoside containing germane and their biological applications are outlined.

APA, Harvard, Vancouver, ISO, and other styles

44

Cobb, Alexander J. A., Antonio Dell’Isola, Ban O. Abdulsattar, Matthew M. W. McLachlan, Benjamin W. Neuman, Christin Müller, Kenneth Shankland, Hawaa M. N. Al-Mulla, Alexander W. D. Binks, and Warren Elvidge. "Synthesis and antiviral activity of novel spirocyclic nucleosides." New Journal of Chemistry 42, no. 22 (2018): 18363–80. http://dx.doi.org/10.1039/c8nj02777c.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Lee, Yoon-Suk, and Byeang Hyean Kim. "Heterocyclic nucleoside analogues: design and synthesis of antiviral, modified nucleosides containing isoxazole heterocycles." Bioorganic & Medicinal Chemistry Letters 12, no. 10 (May 2002): 1395–97. http://dx.doi.org/10.1016/s0960-894x(02)00182-8.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

YOKOZEKI, K., H. SHIRAE, and K. KUBOTA. "ChemInform Abstract: Enzymatic Production of Antiviral Nucleosides by the Application of Nucleoside Phosphorylase." ChemInform 22, no. 36 (August 22, 2010): no. http://dx.doi.org/10.1002/chin.199136092.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Graci, Jason D., Kathleen Too, Eric D. Smidansky, Jocelyn P. Edathil, Eric W. Barr, Daniel A. Harki, Jessica E. Galarraga, et al. "Lethal Mutagenesis of Picornaviruses with N-6-Modified Purine Nucleoside Analogues." Antimicrobial Agents and Chemotherapy 52, no. 3 (March 2008): 971–79. http://dx.doi.org/10.1128/aac.01056-07.

Full text

Abstract:

ABSTRACT RNA viruses exhibit extraordinarily high mutation rates during genome replication. Nonnatural ribonucleosides that can increase the mutation rate of RNA viruses by acting as ambiguous substrates during replication have been explored as antiviral agents acting through lethal mutagenesis. We have synthesized novel N-6-substituted purine analogues with ambiguous incorporation characteristics due to tautomerization of the nucleobase. The most potent of these analogues reduced the titer of poliovirus (PV) and coxsackievirus (CVB3) over 1,000-fold during a single passage in HeLa cell culture, with an increase in transition mutation frequency up to 65-fold. Kinetic analysis of incorporation by the PV polymerase indicated that these analogues were templated ambiguously with increased efficiency compared to the known mutagenic nucleoside ribavirin. Notably, these nucleosides were not efficient substrates for cellular ribonucleotide reductase in vitro, suggesting that conversion to the deoxyriboucleoside may be hindered, potentially limiting genetic damage to the host cell. Furthermore, a high-fidelity PV variant (G64S) displayed resistance to the antiviral effect and mutagenic potential of these analogues. These purine nucleoside analogues represent promising lead compounds in the development of clinically useful antiviral therapies based on the strategy of lethal mutagenesis.

APA, Harvard, Vancouver, ISO, and other styles

48

Schinazi, Raymond F., Grigorii G. Sivets, Mervi A. Detorio, Tami R. McBrayer, Tony Whitaker, Steven J. Coats, and Franck Amblard. "Synthesis and antiviral evaluation of 2′,3′-dideoxy-2′,3′-difluoro-D-arabinofuranosyl 2,6-disubstituted purine nucleosides." Heterocyclic Communications 21, no. 5 (October 1, 2015): 315–27. http://dx.doi.org/10.1515/hc-2015-0174.

Full text

Abstract:

AbstractThe synthesis of new 2,6-disubstituted purine 2′,3′-dideoxy-2′,3′-difluoro-D-arabino nucleosides is reported. Their ability to block HIV and HCV replication along with their cytotoxicity toward Huh-7 cells, human lymphocyte, CEM and Vero cells was also assessed. Among them, β-2,6-diaminopurine nucleoside 25 and guanosine derivative 27 demonstrate potent anti-HIV-1 activity (EC50 = 0.56 and 0.65 μm; EC90 = 4.2 and 3.1 μm) while displaying only moderate cytotoxicity in primary human lymphocytes.

APA, Harvard, Vancouver, ISO, and other styles

49

Meier, Chris. "Nucleoside diphosphate and triphosphate prodrugs – An unsolvable task?" Antiviral Chemistry and Chemotherapy 25, no. 3 (November 3, 2017): 69–82. http://dx.doi.org/10.1177/2040206617738656.

Full text

Abstract:

In this review, our recent advances in the development of nucleoside di- and nucleoside triphosphate prodrugs is summarized. Previously, we had developed a successful membrane-permeable pronucleotide system for the intracellular delivery of nucleoside monophosphates as well, the so-called cycloSal-approach. In contrast to that work in which the delivery is initiated by a chemically driven hydrolysis reaction, for the di- and triphosphate delivery, an enzymatic trigger mechanism involving (carboxy)esterases had to be used. The other features of the new pronucleotide approaches are: (i) lipophilic modification was restricted to the terminal phosphate group leaving charges at the internal phosphate moieties and (ii) appropriate lipophilicity is introduced by long aliphatic residues within the bipartite prodrug moiety. The conceptional design of the di- and triphosphate prodrug systems will be described and the chemical synthesis, the hydrolysis properties, a structure–activity relationship and antiviral activity data will be discussed as well. The advantage of these new approaches is that all phosphorylation steps from the nucleoside analogue into the bioactive nucleoside triphosphate form can be bypassed in the case of the triphosphate prodrugs. Moreover, enzymatic processes like the deamination of nucleosides or nucleoside monophosphates which lead to catabolic clearance of the potential antivirally active compound can be avoided by the delivery of the higher phosphorylated nucleotides.

APA, Harvard, Vancouver, ISO, and other styles

50

Bege, Miklós, Alexandra Kiss, Ilona Bereczki, Jan Hodek, Lenke Polyák, Gábor Szemán-Nagy, Lieve Naesens, Jan Weber, and Anikó Borbás. "Synthesis and Anticancer and Antiviral Activities of C-2′-Branched Arabinonucleosides." International Journal of Molecular Sciences 23, no. 20 (October 19, 2022): 12566. http://dx.doi.org/10.3390/ijms232012566.

Full text

Abstract:

d-Arabinofuranosyl-pyrimidine and -purine nucleoside analogues containing alkylthio-, acetylthio- or 1-thiosugar substituents at the C2’ position were prepared from the corresponding 3’,5’-O-silylene acetal-protected nucleoside 2’-exomethylenes by photoinitiated, radical-mediated hydrothiolation reactions. Although the stereochemical outcome of the hydrothiolation depended on the structure of both the thiol and the furanoside aglycone, in general, high d-arabino selectivity was obtained. The cytotoxic effect of the arabinonucleosides was studied on tumorous SCC (mouse squamous cell) and immortalized control HaCaT (human keratinocyte) cell lines by MTT assay. Three pyrimidine nucleosides containing C2’-butylsulfanylmethyl or -acetylthiomethyl groups showed promising cytotoxicity at low micromolar concentrations with good selectivity towards tumor cells. SAR analysis using a methyl β-d-arabinofuranoside reference compound showed that the silyl-protecting group, the nucleobase and the corresponding C2’ substituent are crucial for the cell growth inhibitory activity. The effects of the three most active nucleoside analogues on parameters indicative of cytotoxicity, such as cell size, division time and cell generation time, were investigated by near-infrared live cell imaging, which showed that the 2’-acetylthiomethyluridine derivative induced the most significant functional and morphological changes. Some nucleoside analogues also exerted anti-SARS-CoV-2 and/or anti-HCoV-229E activity with low micromolar EC50 values; however, the antiviral activity was always accompanied by significant cytotoxicity.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Antiviral nucleosides'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles