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Nucleosides, Nucleotides & Nucleic Acids May 2009In the search for inhibitors of the replication of RNA viruses, including hepatitis C virus (HCV), the hitherto unknown 4'-C-azidomethyl-beta-D-ribofuranosyl nucleosides...
In the search for inhibitors of the replication of RNA viruses, including hepatitis C virus (HCV), the hitherto unknown 4'-C-azidomethyl-beta-D-ribofuranosyl nucleosides of the five naturally occurring nucleic acid bases have been synthesized and their antiviral properties examined. These 4'-C-branched nucleosides were stereospecifically prepared by glycosylation of purine and pyrimidine aglycons with a suitable peracylated 4-C-azidomethyl-D-pentofuranose sugar, followed by removal of the protecting groups. The prepared compounds were tested for their activity against several viruses, but they did not show an antiviral effect.
Topics: Antiviral Agents; Purine Nucleosides; Pyrimidine Nucleosides; RNA Viruses
PubMed: 20183594
DOI: 10.1080/15257770903044531 -
Bioorganic & Medicinal Chemistry Jul 2000As part of our ongoing investigation of the synthesis of biologically interesting 2'-modified-4'-thionucleosides, we synthesized...
As part of our ongoing investigation of the synthesis of biologically interesting 2'-modified-4'-thionucleosides, we synthesized 2'-deoxy-2'-fluoro-4'-thioarabinofuranosylpyrimidine and -purine nucleosides, and evaluated their antiviral and antitumor activities. In the pyrimidine series, beta-anomers of 5-ethyluracil, 5-iodouracil, 5-chloroethyluracil, and 5-iodocytosine derivatives showed potent and selective anti-HSV-1 and HSV-2 activities in vitro. In the purine series, guanine and 2,6-diaminopurine derivatives showed prominent antiviral activities with slight cytotoxicity. On the other hand, the 5-fluorocytosine derivative (5F-4'-thioFAC) showed potent antitumor activity against both leukemia and solid tumor. Its antitumor spectrum against 14 human solid tumor and one leukemic cell lines was compared with that of 4'-thioFAC. The results showed that 5F-4'-thioFAC had an antitumor spectrum similar to that of 4'-thioFAC. However, 5F-4'-thioFAC was about 10 times less active than 4'-thioFAC.
Topics: Antineoplastic Agents; Antiviral Agents; Arabinonucleosides; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Inhibitory Concentration 50; Molecular Structure; Purine Nucleosides; Pyrimidine Nucleosides; Stereoisomerism; Thioglycosides; Tumor Cells, Cultured
PubMed: 10976503
DOI: 10.1016/s0968-0896(00)00065-1 -
European Journal of Medicinal Chemistry Dec 2010Several new purine nucleosides derivatives of allofuranose were prepared according to Vorbrüggen method, starting from 1,2,5,6-di-O-isopropylidene-α-D-allofuranose and...
Several new purine nucleosides derivatives of allofuranose were prepared according to Vorbrüggen method, starting from 1,2,5,6-di-O-isopropylidene-α-D-allofuranose and using 1,2,3,5,6-pentaacetoxy-β-D-allofuranose as key intermediate. The synthesized allofuranosyl nucleosides, as well as some acetyl derivatives, were evaluated for their cytotoxicity in vitro in three human cancer cell lines (MCF-7, Hela-229 and HL-60). Among the studied compounds the 9-(2,3,5,6-tetra-O-acetyl-β-D-allofuranosyl)-2,6-dichloropurine (9) was the most potent one on the three cell lines evaluated, being its activity against HL-60 cells similar to cisplatin.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cisplatin; Cytostatic Agents; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HL-60 Cells; Humans; Molecular Structure; Purine Nucleosides; Stereoisomerism; Structure-Activity Relationship
PubMed: 20934790
DOI: 10.1016/j.ejmech.2010.09.046 -
Journal of Medicinal Chemistry Nov 1977In the first approach by total synthesis to the structure of the antitumor antibiotic septacidin, analogues have been obtained which show similar inhibition of RNA-DNA...
In the first approach by total synthesis to the structure of the antitumor antibiotic septacidin, analogues have been obtained which show similar inhibition of RNA-DNA synthesis in cultured leukemia L1210 cells and similar activity against transplanted leukemia P388 in mice. In these analogues, the natural aminoheptose moiety is replaced by 4-amino-4-deoxy-and 4-amino-4,6-dideoxy-L-glucose, to retain the natural configuration of the pyranose ring. Also retained is the lipophilic fatty acid-amino acid side chain attached to the 4-amino group and glycosylation at the 6-NH2 of adenine. If the fatty acid chain was shortened from C16 to C6, if the fatty chain was shifted to the glycine unit, or if the glycine unit was omitted, activity was completely lost. However, activity was retained if the C16 chain was shortened only to C12 or if the glycine unit was extended to beta-alanine. Both active and inactive analogues were nonbinding to DNA and nonmutagenic to Salmonella strains. The synthetic approach was to start with a suitably protected sugar (L-fucose and L-galactose), construct the adenine moiety at C-1 introduce a 4-amino group, and finally attach the preformed side chain.
Topics: Animals; Antibiotics, Antineoplastic; DNA, Neoplasm; In Vitro Techniques; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Mice; Mutagens; Purine Nucleosides; RNA, Neoplasm; Salmonella; Structure-Activity Relationship
PubMed: 915894
DOI: 10.1021/jm00221a002 -
The Journal of Clinical Investigation May 1956
Topics: Adenosine; Blood Banks; Erythrocytes; Nucleotides; Purine Nucleosides
PubMed: 13319491
DOI: 10.1172/JCI103309 -
Nucleic Acids Symposium Series (2004) 20085-Alkylaminopyrazole nucleosides underwent nitrosation to give the corresponding N1-ribosylated 5-alkyl-amino-4-nitrosopyrazoles. The intramolecular cyclo-dehydration...
5-Alkylaminopyrazole nucleosides underwent nitrosation to give the corresponding N1-ribosylated 5-alkyl-amino-4-nitrosopyrazoles. The intramolecular cyclo-dehydration reactions of these 5-alkylamino-4-nitrosopyrazoles were carried out in pyridine at reflux temperature to afford the ring-closure N-1 ribosylated imidazo[4,5-c]pyrazoles in good yields.
Topics: Bridged Bicyclo Compounds; Purine Nucleosides; Pyrazoles
PubMed: 18776519
DOI: 10.1093/nass/nrn300 -
Molecules (Basel, Switzerland) Feb 2020The enzymatic synthesis of nucleoside analogues has been shown to be a sustainable and efficient alternative to chemical synthesis routes. In this study, dihalogenated...
The enzymatic synthesis of nucleoside analogues has been shown to be a sustainable and efficient alternative to chemical synthesis routes. In this study, dihalogenated nucleoside analogues were produced by thermostable nucleoside phosphorylases in transglycosylation reactions using uridine or thymidine as sugar donors. Prior to the enzymatic process, ideal maximum product yields were calculated after the determination of equilibrium constants through monitoring the equilibrium conversion in analytical-scale reactions. Equilibrium constants for dihalogenated nucleosides were comparable to known purine nucleosides, ranging between 0.071 and 0.081. To achieve 90% product yield in the enzymatic process, an approximately five-fold excess of sugar donor was needed. Nucleoside analogues were purified by semi-preparative HPLC, and yields of purified product were approximately 50% for all target compounds. To evaluate the impact of halogen atoms in positions 2 and 6 on the antiproliferative activity in leukemic cell lines, the cytotoxic potential of dihalogenated nucleoside analogues was studied in the leukemic cell line HL-60. Interestingly, the inhibition of HL-60 cells with dihalogenated nucleoside analogues was substantially lower than with monohalogenated cladribine, which is known to show high antiproliferative activity. Taken together, we demonstrate that thermodynamic calculations and small-scale experiments can be used to produce nucleoside analogues with high yields and purity on larger scales. The procedure can be used for the generation of new libraries of nucleoside analogues for screening experiments or to replace the chemical synthesis routes of marketed nucleoside drugs by enzymatic processes.
Topics: Antineoplastic Agents; HL-60 Cells; Humans; Hydrocarbons, Halogenated; Leukemia; Pentosyltransferases; Purine Nucleosides; Thermodynamics
PubMed: 32093094
DOI: 10.3390/molecules25040934 -
Nucleic Acids Symposium Series (2004) 2008Several thieno-expanded purine nucleoside analogues were synthesized for use as tools in ongoing investigations into nucleic acid structure and function in our...
Several thieno-expanded purine nucleoside analogues were synthesized for use as tools in ongoing investigations into nucleic acid structure and function in our laboratories. The inclusion of the thiophene ring system in the nucleoside endows the purine scaffold with advantages not previously available in other reported expanded purines. The synthesis and preliminary biological studies are reported herein.
Topics: Drug Design; Enzyme Inhibitors; Purine Nucleosides; RNA-Dependent RNA Polymerase
PubMed: 18776540
DOI: 10.1093/nass/nrn321 -
Nature Feb 1978
Topics: Free Radicals; Guanosine; Molecular Conformation; Photochemistry; Purine Nucleosides; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Ultraviolet Rays
PubMed: 625354
DOI: 10.1038/271783a0 -
Journal of Medicinal Chemistry Jan 1990(+-)-cis-[4-[(2,5-Diamino-6-chloropyrimidinyl)amino]-2- cyclopentenyl]carbinol (5a) was synthesized from 2-amino-4,6-dichloropyrimidine and... (Comparative Study)
Comparative Study
(+-)-cis-[4-[(2,5-Diamino-6-chloropyrimidinyl)amino]-2- cyclopentenyl]carbinol (5a) was synthesized from 2-amino-4,6-dichloropyrimidine and cis-4-(hydroxymethyl)cyclopentenylamine (2a) by subsequent preparation of the 5-[(4-chlorophenyl)azo] derivative of the resulting pyrimidine (3a) and reduction of the azo moiety with zinc and acetic acid. The carbocyclic analogue of 2',3'-didehydro-2',3'-dideoxy 2-amino-6-chloropurine (6a) and the corresponding 8-azapurine (9a) were prepared from 5a. The carbocyclic 2',3'-didehydro-2',3'-dideoxy analogues of guanine (7a) and 2,6-diaminopurine (8a), and 8-azaguanine (10a) and 8-aza-2,6-diaminopurine (11a) were prepared from 6a and 9a, respectively. The corresponding 2',3'-saturated series of 2-amino-6-substituted-purine carbocyclic nucleosides was prepared following the same scheme starting with cis-4-(hydroxymethyl)cyclopentylamine (2b). Carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine (carbovir, 7a) emerged as a potent and selective anti-HIV agent. Its hydrolytic stability and its ability to inhibit the infectivity and replication of HIV in T-cells at concentrations of approximately 200-400-fold below toxic concentrations make carbovir an excellent candidate for development as a potential antiretroviral agent.
Topics: Animals; Antiviral Agents; Chemical Phenomena; Chemistry; Cytopathogenic Effect, Viral; Dideoxyadenosine; Dideoxynucleosides; HIV; Leukemia P388; Molecular Structure; Purine Nucleosides; Structure-Activity Relationship; Tumor Cells, Cultured; Virus Replication; Zidovudine
PubMed: 2296018
DOI: 10.1021/jm00163a004