Nucleoside and Nucleotide Analogues for the Treatment of Herpesvirus Infections: Current Stage and New Prospects in the Field of Acyclic Nucleoside Phosphonates

Krečmerová, Marcela

doi:10.5772/27995

Cited by 7 publications

(7 citation statements)

References 77 publications

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“…A great deal of attention was given to the development of HPMPA analogs to improve its pharmacokinetic profile [ 109 ]. Promising anti-DNA virus effects were found for the 2,6-diaminopurine counterpart of HPMPA ( i.e.…”

Section: Inhibitors Of Kshv Lytic Replication Under Investigationmentioning

confidence: 99%

“…, HPMPDAP) and PMEA ( i.e. , PMEDAP) ( Figure 3 ) [ 109 ]. The activity of HPMP-derivatives against DNA viruses is generally higher compared to their counterparts in the PME-series [ 110 ].…”

Section: Inhibitors Of Kshv Lytic Replication Under Investigationmentioning

confidence: 99%

“…A second generation of ANPs has been described including the 6-[2-phosphono-methoxy)alkoxy]-2,4-diaminopyrimidines (DAPy). These compounds fall into two categories with as prototypes ( R )-HPMPO-DAPy and PMEO-DAPy ( Figure 3 ) [ 109 ]. The anti-DNA virus activity of ( R )-HPMPO-DAPy is similar to that of CDV.…”

Section: Inhibitors Of Kshv Lytic Replication Under Investigationmentioning

confidence: 99%

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KSHV Targeted Therapy: An Update on Inhibitors of Viral Lytic Replication

Coen

Duraffour

Snoeck

et al. 2014

Viruses

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Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. Since the discovery of KSHV 20 years ago, there is still no standard treatment and the management of virus-associated malignancies remains toxic and incompletely efficacious. As the majority of tumor cells are latently infected with KSHV, currently marketed antivirals that target the virus lytic cycle have shown inconsistent results in clinic. Nevertheless, lytic replication plays a major role in disease progression and virus dissemination. Case reports and retrospective studies have pointed out the benefit of antiviral therapy in the treatment and prevention of KSHV-associated diseases. As a consequence, potent and selective antivirals are needed. This review focuses on the anti-KSHV activity, mode of action and current status of antiviral drugs targeting KSHV lytic cycle. Among these drugs, different subclasses of viral DNA polymerase inhibitors and compounds that do not target the viral DNA polymerase are being discussed. We also cover molecules that target cellular kinases, as well as the potential of new drug targets and animal models for antiviral testing.

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Section: Inhibitors Of Kshv Lytic Replication Under Investigationmentioning

confidence: 99%

Section: Inhibitors Of Kshv Lytic Replication Under Investigationmentioning

confidence: 99%

Section: Inhibitors Of Kshv Lytic Replication Under Investigationmentioning

confidence: 99%

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KSHV Targeted Therapy: An Update on Inhibitors of Viral Lytic Replication

Coen

Duraffour

Snoeck

et al. 2014

Viruses

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“…Acyclic nucleoside phosphonates (ANPs), such as ( R )-PMPA [9-[9( R )-2-(phosphonomethoxy)propyl]adenine, 1 ] and PMEA [9-[2-(phosphonomethoxy)ethyl] adenine, 2 ] discovered by A. Holý and E. De Clercq in 1986, led to a new family of nucleotide analogs which has attracted considerable attention, [ 1 , 2 , 3 , 4 ]. In order to improve the oral absorption of these phosphonate analogs, ANPs are delivered as prodrugs [ bis (POC)-PMPA ( 3 ) or bis (POM)-PMEA ( 4 )]; prodrug moiety [ 5 ] has previously focused on acyloxyalkyl-ester (pivaloyloxymethyl, POM) [ 6 , 7 ], or (( isopropyloxycarbonyl -oxymethyl)-ester, POC) [ 8 ], alkoxyalkyl groups (hexadecyloxypropyl, HDP) [ 9 ], and more recently on phosphonoamidates (ProTides) [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs

et al. 2021

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A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC50 = 66.4 μM in HepG2 cells, IC50 = 43.1 μM in HepG2 cells) at 10 μM.

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“…Several representatives of this group (acyclovir, ganciclovir, penciclovir) are approved antiviral agents with activity targeted against herpeviruses. The most potent agents were found to be N 9 -alkyl derivatives of adenine with hydroxyl group(s) on the alkyl chain: ( R , S )-3-(adenin-9-yl)-2-hydroxypropanoic acid (AHPA and its alkyl esters), D-eritadenine and the broad-spectrum antiviral agent ( S )-(2,3-dihydroxypropyl)adenine [ 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Lipases as Tools in the Synthesis of Prodrugs from Racemic 9-(2,3-Dihydroxypropyl)adenine

et al. 2012

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Lipases from Geotrichum candidum 4013 (extracellular lipase and cell-bound lipase) were immobilized by adsorption on chitosan beads. The enzyme preparations were tested in the synthesis of ester prodrugs from racemic 9-(2,3-dihydroxypropyl)adenine in dimethylformamide with different vinyl esters (acetate, butyrate, decanoate, laurate, palmitate). The transesterification activities of these immobilized enzymes were compared with commercially available lipases (lipase from hog pancreas, Aspergillus niger, Candida antarctica, Pseudomonas fluorescens). Lipase from Candida antarctica was found to be the most efficient enzyme regarding chemical yield of the desired products, while transesterification by lipase from Aspergillus niger resulted in lower yields.

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Nucleoside and Nucleotide Analogues for the Treatment of Herpesvirus Infections: Current Stage and New Prospects in the Field of Acyclic Nucleoside Phosphonates

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Cited by 7 publications

References 77 publications

KSHV Targeted Therapy: An Update on Inhibitors of Viral Lytic Replication

KSHV Targeted Therapy: An Update on Inhibitors of Viral Lytic Replication

Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs

Lipases as Tools in the Synthesis of Prodrugs from Racemic 9-(2,3-Dihydroxypropyl)adenine

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