Modulation of leukocyte genetic expression by novel purine nucleoside analogs. A new approach to antitumor and antiviral agents

Abstract:Purine nucleoside analogs have been in clinical use for almost 50 years. At the beginning developed as antiviral agents, later their efficacy was demonstrated in cancer treatment, especially hematological malignances. The approval of new purine nucleoside analogs by US Food and Drug Administration (FDA) over the past decade implies that the interest for these drugs still exists. Here, we review new nucleoside analogs that are currently in preclinical or clinical development as anticancer agents. In addition, we highlight the potential for implementation of these drugs in other pathological conditions, particularly in neuroinflammation.

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Metabolism and action of purine nucleoside analogs

Pharmacology & Therapeutics ◽

10.1016/0163-7258(91)90057-s ◽

1991 ◽

Vol 49 (3) ◽

pp. 239-268 ◽

Cited By ~ 94

Author(s):

William Plunkett ◽

Priscilla P. Saunders

Keyword(s):

Nucleoside Analogs ◽

Purine Nucleoside

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Ribavirin

PEDIATRICS ◽

10.1542/peds.79.2.289 ◽

1987 ◽

Vol 79 (2) ◽

pp. 289-291

Author(s):

DAVID ISAACS

Keyword(s):

Thymidine Kinase ◽

Antibacterial Agents ◽

Antiviral Agents ◽

Nucleoside Analogs ◽

Viral Diseases ◽

Herpes Viruses ◽

Important Advance ◽

Dna Viruses ◽

Low Toxicity ◽

Simplex Virus

Immunization has proved to be the most effective way of controlling viral diseases, and the development of antiviral drugs has lagged behind the development of antibacterial agents. Many of the early antiviral agents were DNA nucleoside analogs such as idoxuridine, cytarabine, and vidarabine, which competitively inhibited replication of DNA viruses, especially herpes viruses. An important advance was the deliberate synthesis of a purine nucleoside analog, acyclovir, which is only active following phosphorylation, which is carried out selectively by virus-coded thymidine kinase. Acyclovir is active against some herpesviruses, particularly herpes simplex virus, but not against RNA viruses, and appears to have low toxicity because of the low level of phosphorylation by host cell thymidine kinase.

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Potential Immunological Action of Purine Nucleoside Analogs

Acute Leukemias VI - Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ◽

10.1007/978-3-642-60377-8_58 ◽

1997 ◽

pp. 358-366

Author(s):

G. Dighiero

Keyword(s):

Nucleoside Analogs ◽

Purine Nucleoside

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Assessment of microRNA expression in leukemic cells as predictors of sensitivity to purine nucleoside analogs, fludarabine and cladribine, in chronic lymphocytic leukemia patients

Cancer Management and Research ◽

10.2147/cmar.s191311 ◽

2019 ◽

Vol Volume 11 ◽

pp. 5021-5031

Author(s):

Agnieszka Szymczyk ◽

Sylwia Chocholska ◽

Arkadiusz Macheta ◽

Dariusz Szczepanek ◽

Marek Hus ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Nucleoside Analogs ◽

Microrna Expression ◽

Lymphocytic Leukemia ◽

Purine Nucleoside ◽

Leukemic Cells

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Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00397-19 ◽

2019 ◽

Vol 63 (7) ◽

Cited By ~ 3

Author(s):

Keivan Zandi ◽

Leda Bassit ◽

Franck Amblard ◽

Bryan D. Cox ◽

Pouya Hassandarvish ◽

...

Keyword(s):

Japanese Encephalitis ◽

Viral Infections ◽

Antiviral Agents ◽

Public Health Problem ◽

Nucleoside Analogs ◽

Global Public Health ◽

Direct Acting Antiviral ◽

East And Southeast Asia ◽

Direct Acting ◽

Global Public Health Problem

ABSTRACTDengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from theFlaviviridaefamily. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world’s population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2′-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.

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