scholarly journals Synthesis and antiviral properties of 1-substituted 3-[ω-(4-oxoquinazolin-4(3h)-yl)alkyl]uracil derivatives

Acta Naturae ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 134-139
Author(s):  
Maria P. Paramonova ◽  
Anastasia L. Khandazhinskaya ◽  
Alexander A. Ozerov ◽  
Sergey N. Kochetkov ◽  
Robert Snoeck ◽  
...  
Keyword(s):  
Cell Culture ◽  
Nitrogen Atom ◽  
Varicella Zoster Virus ◽  
Human Cytomegalovirus ◽  
Inhibitory Activity ◽  
Antiviral Agents ◽  
Pyrimidine Ring ◽  
Methylene Bridge ◽  
Varicella Zoster ◽  
Uracil Derivatives

А series of uracil derivatives containing a 4-oxoquinazoline fragment bound to the nitrogen atom N3 of the pyrimidine ring by a short methylene bridge was synthesized to search for new antiviral agents. Some compounds in this series are shown to exhibit high inhibitory activity against human cytomegalovirus and the varicella zoster virus in a HEL cell culture.

scholarly journals 2-(2,4-Dioxy-1,2,3,4-Tetrahydropyrimidin-1-yl)-N-(4-Phenoxyphenyl)-Acetamides as a Novel Class of Cytomegalovirus Replication Inhibitors

Acta Naturae ◽  
2015 ◽  
Vol 7 (4) ◽  
pp. 142-145 ◽  
Author(s):  
D. A. Babkov ◽  
M. P. Paramonova ◽  
A. A. Ozerov ◽  
A. L. Khandazhinskaya ◽  
R. Snoeck ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Varicella Zoster Virus ◽  
Cell Cultures ◽  
Human Cytomegalovirus ◽  
Inhibitory Activity ◽  
Pyrimidine Ring ◽  
The Novel ◽  
Varicella Zoster ◽  
Uracil Derivatives

A series of novel uracil derivatives, bearing N-(4-phenoxyphenyl)acetamide moiety at N3 of a pyrimidine ring, has been synthesized. Their antiviral activity has been evaluated. It has been found that the novel compounds possess high inhibitory activity against replication of human cytomegalovirus (AD-169 and Davis strains) in HEL cell cultures. In addition, some of the derivatives proved to be inhibitory against varicella zoster virus.

Synthesis and biological evaluation of 5-(alkyn-1-yl)-1-(p-toluenesulfonyl)uracil derivatives

2006 ◽  
Vol 84 (4) ◽  
pp. 580-586 ◽  
Author(s):  
Zlatko Janeba ◽  
Jan Balzarini ◽  
Graciela Andrei ◽  
Robert Snoeck ◽  
Erik De Clercq ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Human Cytomegalovirus ◽  
Biological Evaluation ◽  
Sonogashira Coupling ◽  
Terminal Alkynes ◽  
Pyrimidine Derivatives ◽  
Varicella Zoster ◽  
Uracil Derivatives ◽  
Synthesis And Biological Evaluation

Sonogashira coupling of 5-iodouracil (2) and trimethylsilylacetylene gave 5-(trimethylsilylethynyl)uracil (3), which was deprotected to give 5-ethynyluracil (4). Copper(I)-catalyzed cyclization of 4 gave furo[2,3-d]pyrimidin-2(3H)-one (5). Tosylation of 2 and 4 gave the 1-(p-toluenesulfonyl) derivatives 6 and 7, respectively. The tosylated compound 6 and trimethylsilylacetylene did not undergo Sonogashira coupling, and copper(I)-catalyzed cyclization of 7 did not occur. Coupling of 2 with several terminal alkynes gave 5-(alkyn-1-yl)uracil derivatives (9), which underwent tosylation to produce the targeted 5-(alkyn-1-yl)-1-(p-toluenesulfonyl)uracil compounds (11). Copper(I)-catalyzed cyclization of 9 gave the respective furopyrimidines (10) in low yields. Again, cyclization did not occur with the tosyl derivatives (11). Activity against varicella-zoster virus (VZV) was observed with longer-chain analogues of 9 and 11, and compound 7 showed activity against human cytomegalovirus (HCMV) at near cytotoxic levels.Key words: antiviral screening, furo[2,3-d]pyrimidin-2(3H)-one derivatives, Sonogashira coupling, 1-(p-toluenesulfonyl)pyrimidine derivatives.

Synthesis and Antiviral Activities of 3-Aralkyl-Thiomethylimidazo[1,2-b]Pyridazine Derivatives

2003 ◽  
Vol 14 (4) ◽  
pp. 177-182 ◽  
Author(s):  
Christophe Galtier ◽  
Sylvie Mavel ◽  
Robert Snoeck ◽  
Graciela Andreï ◽  
Christophe Pannecouque ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Varicella Zoster Virus ◽  
Human Cytomegalovirus ◽  
Antiviral Agents ◽  
Varicella Zoster ◽  
Immunodeficiency Virus ◽  
Antiviral Activities ◽  
Pyridazine Derivatives

The synthesis of novel substituted 3-aralkylth-iomethylimidazo[1,2- b]pyridazines is reported. All of the synthesized compounds are devoid of antiviral activity against the replication of human immunodeficiency virus. However, compounds 6-chloro-8-methyl-3-phenethylthioimidazo[1,2- b]pyridazine and 6-chloro-2-methyl-3-phenethyl-thioimidazo[1,2- b]pyridazine are potent inhibitors of the replication of human cytomegalovirus in vitro, while compounds 6-chloro-2-methyl-3-benzylthiomethylimidazo[1,2- b]pyridazine and 6-chloro-2-methyl-3-phenethyl-thioimidazo[1,2- b]pyridazineare inhibitors of the replication of varicella-zoster virus. The results presented here suggest that compound 10 should be considered as a new lead in the development of antiviral agents.

scholarly journals A Novel Human Skin Tissue Model To Study Varicella-Zoster Virus and Human Cytomegalovirus

2020 ◽  
Vol 94 (22) ◽  
Author(s):  
Megan G. Lloyd ◽  
Nicholas A. Smith ◽  
Michael Tighe ◽  
Kelsey L. Travis ◽  
Dongmei Liu ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Human Skin ◽  
Mouse Models ◽  
Human Cytomegalovirus ◽  
Fetal Tissue ◽  
Target Cells ◽  
Varicella Zoster ◽  
Adult Human ◽  
Infected Cells ◽  
Adult Human Skin

ABSTRACT The herpesviruses varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) are endemic to humans. VZV causes varicella (chicken pox) and herpes zoster (shingles), while HCMV causes serious disease in immunocompromised patients and neonates. More effective, less toxic antivirals are needed, necessitating better models to study these viruses and evaluate antivirals. Previously, VZV and HCMV models used fetal tissue; here, we developed an adult human skin model to study VZV and HCMV in culture and in vivo. While VZV is known to grow in skin, it was unknown whether skin could support an HCMV infection. We used TB40/E HCMV and POka VZV strains to evaluate virus tropism in skin organ culture (SOC) and skin xenograft mouse models. Adult human skin from reduction mammoplasties was prepared for culture on NetWells or mouse implantation. In SOC, VZV infected the epidermis and HCMV infected the dermis. Specifically, HCMV infected fibroblasts, endothelial cells, and hematopoietic cells, with some infected cells able to transfer infection. VZV and HCMV mouse models were developed by subcutaneous transplantation of skin into SCID/beige or athymic nude mice at 2 independent sites. Viruses were inoculated directly into one xenograft, and widespread infection was observed for VZV and HCMV. Notably, we detected VZV- and HCMV-infected cells in the contralateral, uninoculated xenografts, suggesting dissemination from infected xenografts occurred. For the first time, we showed HCMV successfully grows in adult human skin, as does VZV. Thus, this novel system may provide a much-needed preclinical small-animal model for HCMV and VZV and, potentially, other human-restricted viruses. IMPORTANCE Varicella-zoster virus and human cytomegalovirus infect a majority of the global population. While they often cause mild disease, serious illness and complications can arise. Unfortunately, there are few effective drugs to treat these viruses, and many are toxic. To complicate this, these viruses are restricted to replication in human cells and tissues, making them difficult to study in traditional animal models. Current models rely heavily on fetal tissues, can be prohibitively expensive, and are often complicated to generate. While fetal tissue models provide helpful insights, it is necessary to study human viruses in human tissue systems to fully understand these viruses and adequately evaluate novel antivirals. Adult human skin is an appropriate model for these viruses because many target cells are present, including basal keratinocytes, fibroblasts, dendritic cells, and lymphocytes. Skin models, in culture and xenografts in immunodeficient mice, have potential for research on viral pathogenesis, tissue tropism, dissemination, and therapy.

scholarly journals Potent β-Lactam Inhibitors of Human Cytomegalovirus Protease

1998 ◽  
Vol 9 (5) ◽  
pp. 379-387 ◽  
Author(s):  
C Yoakim ◽  
WW Ogilvie ◽  
DR Cameron ◽  
C Chabot ◽  
C Grand-Maître ◽  
...  
Keyword(s):  
Cell Culture ◽  
Antiviral Activity ◽  
Human Cytomegalovirus ◽  
Inhibitory Activity ◽  
Enzymatic Assay ◽  
Side Chain ◽  
Plaque Reduction Assay ◽  
Reduction Assay ◽  
Culture Activity

A series of novel monobactam inhibitors of human cytomegalovirus (HCMV) protease has been described that possess a heterocyclic thiomethyl side chain at C-4. Changes to the heterocycle did not significantly change the inhibitory activity of these compounds in an enzymatic assay, although improvements in solubility and cell culture activity were noted. A number of permutations between C-4 substitutions and N-1 derivatives led to the identification of several β-lactams with antiviral activity in a plaque reduction assay. N-methyl thiotetrazole-containing compounds were found to be the most potent inhibitors in the enzymatic assay.

Genotyping of varicella-zoster virus strains after serial passages in cell culture

2007 ◽  
Vol 145 (1) ◽  
pp. 80-83 ◽  
Author(s):  
Andreas Sauerbrei ◽  
Anja Philipps ◽  
Roland Zell ◽  
Peter Wutzler
Keyword(s):  
Cell Culture ◽  
Varicella Zoster Virus ◽  
Varicella Zoster ◽  
Virus Strains

scholarly journals Inhibiting effect of (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine on varicella-zoster virus replication in cell culture.

1987 ◽  
Vol 31 (1) ◽  
pp. 76-80 ◽  
Author(s):  
G Abele ◽  
A Karlstrom ◽  
J Harmenberg ◽  
S Shigeta ◽  
A Larsson ◽  
...  
Keyword(s):  
Cell Culture ◽  
Varicella Zoster Virus ◽  
Virus Replication ◽  
Varicella Zoster ◽  
Inhibiting Effect

scholarly journals Glycoprotein I of Varicella-Zoster Virus Is Required for Viral Replication in Skin and T Cells

2002 ◽  
Vol 76 (16) ◽  
pp. 8468-8471 ◽  
Author(s):  
Jennifer Moffat ◽  
Hideki Ito ◽  
Marvin Sommer ◽  
Shannon Taylor ◽  
Ann M. Arvin
Keyword(s):  
Cell Culture ◽  
T Cells ◽  
Viral Replication ◽  
Varicella Zoster Virus ◽  
Human Skin ◽  
Deletion Mutant ◽  
Varicella Zoster ◽  
Glycoprotein I

ABSTRACT Varicella-zoster virus (VZV) glycoprotein I (gI) is dispensable in cell culture; the SCIDhu model of VZV pathogenesis was used to determine whether gI is necessary in vivo. The parental and repaired viruses grew in human skin and thymus/liver implants, but the gI deletion mutant was not infectious. Thus, gI is essential for VZV infectivity in skin and T cells.

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