scholarly journals Synthesis and Anti-HIV Activity of Guanine Modified Fluorinated Acyclic Nucleoside Phosphonate Derivatives

2019 ◽  
Vol 16 (2) ◽  
pp. e1800532 ◽  
Author(s):  
Min Luo ◽  
Elisabetta Groaz ◽  
Steven De Jonghe ◽  
Dominique Schols ◽  
Piet Herdewijn
Keyword(s):  
Acyclic Nucleoside ◽  
Anti Hiv ◽  
Acyclic Nucleoside Phosphonate

scholarly journals In-silico designing of acyclic nucleoside phosphonates and their anti-HIV potential

2012 ◽  
Vol 12 (Suppl 1) ◽  
pp. P3
Author(s):  
Dipti Yadav ◽  
Anuradha Singh ◽  
Madhu Yadav ◽  
Ramendra K Singh
Keyword(s):  
In Silico ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Anti Hiv

Inhibitory Effects of Acyclic Nucleoside Phosphonate Analogues on Hepatitis B Virus DNA Synthesis in HB611 Cells

1994 ◽  
Vol 5 (2) ◽  
pp. 57-63 ◽  
Author(s):  
T. Yokota ◽  
K. Konno ◽  
S. Shigeta ◽  
A. Holy ◽  
J. Balzarini ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Synthesis ◽  
Dna Polymerase ◽  
Hbv Dna ◽  
Inhibitory Effects ◽  
B Virus ◽  
Acyclic Nucleoside ◽  
Cellular Dna ◽  
Acyclic Nucleoside Phosphonate

By using an assay system based on a human hepatoblastoma cell line (HB611) that continuously synthesizes hepatitis B virus (HBV) DNA, 56 acyclic nucleoside phosphonate analogues were examined for their inhibitory effects on HBV DNA synthesis. The following compounds were found to inhibit HBV DNA synthesis at concentrations that were significantly lower than their minimum cytotoxic concentrations; 9-(2-phosphonylmethoxyethyl)adenine (PMEA), 9-(2-phosphonylmethoxyethyl) guanine(PMEG), 9-(2-phosphonylmethoxyethyl) guanine ethyl ester (PMEGEE), 9 - (2 - phosphonylmethoxyethyl) - 1 - deazaadenine (PMEC1A), 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), ( S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA), 9-(3-isopropoxy-2-phosphonylmethoxypropyl)adenine (IPPMPA), 9-( RS)-(2-phosphonylmethoxypropyl)adenine (PMPA) and 9-(3-hydroxy-2-phosphonylmethoxypropyl)-2, 6-diaminopurine (HPMPDAP). The most selective compounds (with indexes greater than 100) were PMEDAP, PMEA, IPPMPA, and PMPA. Acyclic pyrimidine nucleoside phosphonate analogues did not prove markedly selective as anti-HBV agents. Diphosphoryl derivatives of some acyclic purine nucleoside phos-phonates (i.e. PMEA, PMEDAP, HPMPA) were prepared. They proved inhibitory to HBV DNA polymerase but not cellular DNA polymerase α.

Discovery of an Acyclic Nucleoside Phosphonate that InhibitsMycobacterium tuberculosisThyX Based on the Binding Mode of a 5-Alkynyl Substrate Analogue

ChemMedChem ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. 1373-1383 ◽  
Author(s):  
Anastasia Parchina ◽  
Matheus Froeyen ◽  
Lia Margamuljana ◽  
Jef Rozenski ◽  
Steven De Jonghe ◽  
...  
Keyword(s):  
Binding Mode ◽  
Substrate Analogue ◽  
Acyclic Nucleoside ◽  
Acyclic Nucleoside Phosphonate

scholarly journals Inhibitory Effects of Novel Nucleoside and Nucleotide Analogues on Epstein—Barr Virus Replication

1998 ◽  
Vol 9 (3) ◽  
pp. 275-282 ◽  
Author(s):  
A Meerbach ◽  
A Holý ◽  
P Wutzler ◽  
E De Clercq ◽  
J Neyts
Keyword(s):  
Dna Hybridization ◽  
Epstein Barr Virus ◽  
Inhibitory Effects ◽  
Nucleotide Analogues ◽  
Barr Virus ◽  
Ebv Dna ◽  
Acyclic Nucleoside ◽  
Epstein Barr ◽  
New Compounds ◽  
Acyclic Nucleoside Phosphonate

The anti-Epstein–Barr virus (EBV) activity of different classes of compounds was assessed by means of an EBV DNA hybridization assay using a digoxigenin-labelled probe specific for the BamHI W fragment of the EBV genome, as well as by measuring viral capsid antigen (VCA) expression after a 7 day incubation period of P3HR-1 producer cells with the test substances. Acyclovir, ganciclovir, cidofovir and zidovudine were included as reference compounds. Several compounds proved to be potent and selective inhibitors of EBV DNA synthesis and VCA expression. Of the new compounds that were evaluated for their anti-EBV activity, the highest efficacy (lowest EC50) and highest selectivity index (SI) were shown by the purine nucleoside analogue 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S2242) (EC50 0.6 ng/ml; SI 600), the acyclic nucleoside phosphonate analogues 9-(2-phosphonomethoxyethyl)-6-dimethylaminopurine (EC50 1.1 μg/ml; SI 91), 9-(2-phosphonomethoxyethyl)-2-amino-6-benzhydrylaminopurine (EC501.3 μg/ml; SI 29), 7-(2-phosphonomethoxyethyl)-6-dimethylaminopurine (EC50 0.8 μg/ml; SI 56), 9-( R)-(2-phosphonomethoxypropyl)-6-(2-dimethylaminoethyl)-aminopurine (EC50 0.5 μg/ml; SI 42), the 2′,3′-dideoxythymidine derivative 3′-oximino-2′,3′-dideoxythymidine (EC501.5 μg/ml; SI 65), and 1-(2,3-dideoxy-3- N-hydroxyamino-β-d-threo-pentafuran yl)pentafuranosyl)thymine (EC50 4.1 μg/ml; SI >24).

New strategies in synthesis of acyclic nucleoside phosphonate prodrugs

2011 ◽  
Author(s):  
Marcela Krečmerová ◽  
Tomáš Tichý ◽  
Jiří Blažek ◽  
Karel Pomeisl
Keyword(s):  
Acyclic Nucleoside ◽  
Acyclic Nucleoside Phosphonate ◽  
New Strategies

Interaction of Phosphates of the Acyclic Nucleoside Phosphonates with Nucleoside Diphosphate Kinase from Yeast and Bovine Liver

2006 ◽  
Vol 71 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Květoslava Horská ◽  
Ivan Votruba ◽  
Antonín Holý
Keyword(s):  
Nucleoside Diphosphate Kinase ◽  
Bovine Liver ◽  
Kinetic Constants ◽  
Aliphatic Chain ◽  
Ndp Kinase ◽  
Hydroxymethyl Group ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Acyclic Nucleoside Phosphonate

The ability of monophosphates of selected acyclic nucleoside phosphonates to serve as substrates for the title NDP kinases was studied. Comparison of the kinetic constants (KM, Vmax, kcat and kcat/KM) estimates indicates that the yeast enzyme catalyzes the phosphorylation of purine and pyrimidine acyclic nucleoside phosphate phosphonates of the 9-[2-(phosphonomethoxy)ethyl] and/or 9-[2-(phosphonomethoxy)propyl] series more efficiently than bovine liver NDP kinase. Yeast enzyme preferentially phosphorylates phosphates of the (phosphono- methoxyalkyl)guanines rather than their adenine counterparts; both enzymes phosphorylate R-enantiomers of the 9-[2-(phosphonomethoxy)propyl] series more efficiently than the corresponding S-enantiomers. Substitution of the aliphatic chain at the position 3 with hydroxymethyl group considerably increases the substrate activity of phosphate of acyclic nucleoside phosphonate. The resulting substrate activity (kcat/KM ratio) of all acyclic nucleoside phosphonate phosphates studied is three to five orders of magnitude lower than that for natural NDPs.

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