scholarly journals Synthesis and Antiviral Evaluation of 3′-Fluoro-5′-norcarbocyclic Nucleoside Phosphonates Bearing Uracil and Cytosine as Potential Antiviral Agents

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3708
Author(s):  
Pierre-Yves Geant ◽  
Jean-Pierre Uttaro ◽  
Christian Périgaud ◽  
Christophe Mathé
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Antiviral Agents ◽  
Nucleoside Analogues ◽  
Viral Diseases ◽  
Heterocyclic Base ◽  
Immunodeficiency Virus ◽  
Pyrimidine Bases ◽  
Carbocyclic Nucleoside

Carbocyclic nucleoside analogues are an essential class of antiviral agents and are commonly used in the treatment of viral diseases (hepatitis B, AIDS). Recently, we reported the racemic synthesis and the anti-human immunodeficiency virus activities (HIV) of 3′-fluoro-5′-norcarbocyclic nucleoside phosphonates bearing purines as heterocyclic base. Based on these results, the corresponding racemic norcarbocyclic nucleoside phosphonates bearing pyrimidine bases were synthesized. The prepared compounds were evaluated against HIV, but none of them showed marked antiviral activity compared to their purine counterparts.

scholarly journals Synthesis of 4′-Substituted-2′-Deoxy-2′-α-Fluoro Nucleoside Analogs as Potential Antiviral Agents

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1258
Author(s):  
Mahesh Kasthuri ◽  
Chengwei Li ◽  
Kiran Verma ◽  
Olivia Ollinger Russell ◽  
Lyndsey Dickson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Respiratory Syncytial Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Rna Viruses ◽  
Antiviral Agents ◽  
Nucleoside Analogs ◽  
Viral Diseases ◽  
Immunodeficiency Virus ◽  
Syncytial Virus

Nucleoside analogs are widely used for the treatment of viral diseases (Hepatitis B/C, herpes and human immunodeficiency virus, HIV) and various malignancies. ALS-8176, a prodrug of the 4′-chloromethyl-2′-deoxy-2′-fluoro nucleoside ALS-8112, was evaluated in hospitalized infants for the treatment of respiratory syncytial virus (RSV), but was abandoned for unclear reasons. Based on the structure of ALS-8112, a series of novel 4′-modified-2′-deoxy-2′-fluoro nucleosides were synthesized. Newly prepared compounds were evaluated against RSV, but also against a panel of RNA viruses, including Dengue, West Nile, Chikungunya, and Zika viruses. Unfortunately, none of the compounds showed marked antiviral activity against these viruses.

Zidovudine and Didanosine Combination Therapy in Children With Human Immunodeficiency Virus Infection

PEDIATRICS ◽  
1994 ◽  
Vol 93 (2) ◽  
pp. 316-322 ◽  
Author(s):  
Robert N. Husson ◽  
Brigitta U. Mueller ◽  
Maureen Farley ◽  
Linda L. Lewis ◽  
Frank M. Balis ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Combination Therapy ◽  
Antiviral Activity ◽  
Hiv Infection ◽  
Geometric Mean ◽  
Single Agent ◽  
Nucleoside Analogues ◽  
Hematologic Toxicity ◽  
Immunodeficiency Virus

Objective. Zidovudine and didanosine are both beneficial for the treatment of human immunodeficiency virus (HIV) infection in children. Because disease progression and toxicity often limit their long-term use as single agents, new approaches to using nucleoside analogues are necessary to improve current antiretroviral therapy. Design. We conducted a phase I-II study to evaluate the tolerance, pharmacokinetics, and antiviral activity of the combination of zidovudine and didanosine in children with HIV infection. Sixty-eight children who were either previously untreated or who had manifested hematologic toxicity on full-dose zidovudine were enrolled. Eight dose combinations were studied in the previously untreated children, with doses of zidovudine ranging from 90 to 180 mg/m2 every 6 hours and doses of didanosine ranging from 90 to 180 mg/m2 every 12 hours. Results. Fifty-four previously untreated HIV-infected children were enrolled in this part of the study, of whom 49 remained in the study for a minimum of 24 weeks. For children with previous zidovudine-related hematologic toxicity, three dose levels with zidovudine at 60 mg/m2 every 6 hours orally and didanosine ranging from 90 to 180 mg/m2 every 12 hours orally were used. A total of 14 children were enrolled in this part of the study, and 12 remained on therapy for at least 24 weeks. No evidence of new or enhanced toxicity was observed in either group. After 24 weeks, the median CD4 cell count for all patients increased from 331 to 556 cells/mm3 (P = .01). For the previously untreated group, the median increase in CD4 counts was from 386 to 726 cells/mm3 (P = .003). The median p24 antigen concentration (in those with a detectable level at baseline) decreased from 95 to <31 pg/mL (P < .001). The geometric mean titer of HIV in plasma decreased from 83.1 to 2.7 tissue culture infectious doses/mL (P = .001). Conclusions. The combination of zidovudine and didanosine was well-tolerated at doses as high as those used in single agent therapy. Potent in vivo antiviral activity was observed. Combination therapy with nucleoside analogues may be an important approach to optimizing the use of these agents in the treatment of HIV infection.

scholarly journals Efficiency of nanoparticles as a carrier system for antiviral agents in human immunodeficiency virus-infected human monocytes/macrophages in vitro.

1996 ◽  
Vol 40 (6) ◽  
pp. 1467-1471 ◽  
Author(s):  
A R Bender ◽  
H von Briesen ◽  
J Kreuter ◽  
I B Duncan ◽  
H Rübsamen-Waigmann
Keyword(s):  
Aqueous Solution ◽  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Drug Carrier ◽  
Antiviral Agents ◽  
Human Monocytes ◽  
Carrier System ◽  
Antigen Production ◽  
Immunodeficiency Virus

Polyhexylcyanoacrylate nanoparticles loaded with either the human immunodeficiency virus (HIV) protease inhibitor saquinavir (Ro 31-8959) or the nucleoside analog zalcitabine (2',3'-dideoxycytidine) were prepared by emulsion polymerization and tested for antiviral activity in primary human monocytes/macrophages in vitro. Both nanoparticulate formulations led to a dose-dependent reduction of HIV type 1 antigen production. While nanoparticle-bound zalcitabine showed no superiority to an aqueous solution of the drug, a significantly higher efficacy was observed with saquinavir-loaded nanoparticles. In acutely infected cells, an aqueous solution of saquinavir showed little antiviral activity at concentrations below 10 nM, whereas the nanoparticulate formulation exhibited a good antiviral effect at a concentration of 1 nM and a still-significant antigen reduction at 0.1 nM (50% inhibitory concentrations = 4.23 nM for the free drug and 0.39 nM for the nanoparticle-bound drug). At a concentration of 100 nM, saquinavir was completely inactive in chronically HIV-infected macrophages, but when bound to nanoparticles it caused a 35% decrease in antigen production. Using nanoparticles as a drug carrier system could improve the delivery of antiviral agents to the mononuclear phagocyte system in vivo, overcoming pharmacokinetic problems and enhancing the activities of drugs for the treatment of HIV infection and AIDS.

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.

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