Synthesis, antiviral activity, cytotoxicity and cellular pharmacology of l-3'-azido-2',3'-dideoxypurine nucleosides. 2011

Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine, and the Veterans Affairs Medical Center, Decatur, GA 30033, USA.

Microwave-assisted optimized transglycosylation reactions were used to prepare eleven modified l-3'-azido-2',3'-dideoxypurine nucleosides. These l-nucleoside analogs were evaluated against HIV and hepatitis B virus. The l-3'-azido-2',3'-dideoxypurines nucleosides were metabolized to nucleoside 5'-triphosphates in primary human lymphocytes, but exhibited weak or no antiviral activity against HIV-1. The nucleosides were also inactive against HBV in HepG2 cells. Pre-steady state kinetic experiments demonstrated that the l-3'-azido-2',3'-dideoxypurine triphosphates could be incorporated by purified HIV-1 reverse transcriptase, although their catalytic efficiency (k(pol)/K(d)) of incorporation was low. Interestingly, a phosphoramidate prodrug of l-3'-azido-2',3'-dideoxyadenosine exhibited anti-HIV-1 activity without significant toxicity.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D008872 Microwaves That portion of the electromagnetic spectrum from the UHF (ultrahigh frequency) radio waves and extending into the INFRARED RAYS frequencies. EHF Waves,Extremely High Frequency Radio Waves,Micro Wave,Micro Waves,Ultrahigh Frequency Waves,Microwave Radiation,EHF Wave,Micro Waves,Microwave,Microwave Radiations,Radiation, Microwave,Ultrahigh Frequency Wave,Wave, EHF,Wave, Micro,Wave, Ultrahigh Frequency,Waves, Micro
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D006515 Hepatitis B virus The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum. Dane Particle,Hepatitis Virus, Homologous Serum,B virus, Hepatitis,Hepatitis B viruses,Particle, Dane,viruses, Hepatitis B
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
September 2009, Antimicrobial agents and chemotherapy,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
January 2001, Nucleosides, nucleotides & nucleic acids,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
June 1990, Journal of medicinal chemistry,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
January 1991, Nucleic acids symposium series,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
February 2001, Bioorganic & medicinal chemistry letters,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
January 2005, Nucleosides, nucleotides & nucleic acids,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
March 1985, Journal of pharmaceutical sciences,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
June 2005, Journal of medicinal chemistry,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
August 1998, Nucleosides & nucleotides,
Hong-Wang Zhang, and Mervi Detorio, and Brian D Herman, and Sarah Solomon, and Leda Bassit, and James H Nettles, and Aleksandr Obikhod, and Si-Jia Tao, and John W Mellors, and Nicolas Sluis-Cremer, and Steven J Coats, and Raymond F Schinazi
May 2009, Nucleosides, nucleotides & nucleic acids,
Copied contents to your clipboard!