BIOMAT Database Logo BIOMAT Database Logo

Activities of masked 2',3'-dideoxynucleoside monophosphate derivatives against human immunodeficiency virus in resting macrophages. 2000

S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.

The anti-human immunodeficiency virus (HIV) activity of aryloxyphosphoramidate protides of a number of anti-HIV nucleoside analogues was assessed in resting primary monocyte-macrophages (M/M). While 2',3'-dideoxythymidine (d4T), 2',3'-dideoxyadenosine (ddA), and 2',3'-dideoxy-2',3'-didehydroadenosine (d4A) protides showed an anti-HIV activity that was 25- to 625-fold greater than the parent nucleotides d4T, ddA, and d4A, respectively, other aryloxyphosphoramidate protides showed similar or even lower anti-HIV activities than their parent compounds. This variable anti-HIV effect is most likely related to the different dynamics of intracellular nucleoside monophosphate release from the protides. Our results indicate the potential advantage of therapeutic use of this approach for some nucleotide analogues to affect HIV replication in M/M, one of the major reservoirs of HIV in vivo.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015224 Dideoxynucleosides Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription. 2',3'-Dideoxynucleosides,Dideoxyribonucleosides,ddNus,2',3' Dideoxynucleosides
D016048 Dideoxyadenosine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to DIDANOSINE (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite. 2',3'-Dideoxyadenosine,ddA (Antiviral),2',3' Dideoxyadenosine
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV

Related Publications

S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Anti-human immunodeficiency virus type 1 activities of dideoxynucleoside phosphotriester derivatives in primary monocytes/macrophages.
January 1996, Research in virology,
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Decreased anti-human immunodeficiency virus type-1 activities of 2',3'-dideoxynucleoside analogs in MOLT-4 cell sublines resistant to 2',3'-dideoxynucleoside analogs.
October 1993, Acta virologica,
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Disparate actions of hydroxyurea in potentiation of purine and pyrimidine 2',3'-dideoxynucleoside activities against replication of human immunodeficiency virus.
August 1995, Proceedings of the National Academy of Sciences of the United States of America,
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Divergent anti-human immunodeficiency virus activity and anabolic phosphorylation of 2',3'-dideoxynucleoside analogs in resting and activated human cells.
April 1994, The Journal of biological chemistry,
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Marked inhibitory activity of masked aryloxy aminoacyl phosphoramidate derivatives of dideoxynucleoside analogues against visna virus infection.
April 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association,
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Sustainable Protocol for the Synthesis of 2',3'-Dideoxynucleoside and 2',3'-Didehydro-2',3'-dideoxynucleoside Derivatives.
June 2022, Molecules (Basel, Switzerland),
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Comparative analysis of anti-human immunodeficiency virus type 1 activities of dideoxynucleoside analogs in resting and activated peripheral blood mononuclear cells.
November 1995, Antimicrobial agents and chemotherapy,
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
[Inhibition of reproduction of the human immunodeficiency virus in cell culture by 2',3'-dideoxynucleoside-5'-phosphites].
January 1992, Molekuliarnaia biologiia,
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Removal of anti-human immunodeficiency virus 2',3'-dideoxynucleoside monophosphates from DNA by a novel human cytosolic 3'-->5' exonuclease.
September 1995, Biochemical pharmacology,
S Aquaro, and O Wedgwood, and C Yarnold, and D Cahard, and R Pathinara, and C McGuigan, and R Calio', and E de Clercq, and J Balzarini, and C F Perno
Activities of (-)-carbovir and 3'-azido-3'-deoxythymidine against human immunodeficiency virus in vitro.
June 1990, Antimicrobial agents and chemotherapy,
Copied contents to your clipboard!