BIOMAT Database Logo BIOMAT Database Logo

Synthesis and anti-HIV activity of novel 2',3'-dideoxy-3'-thiacytidine prodrugs. 2009

Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
Departamento de Farmacia, Facultad de Ciencias Químicas, Ciudad Universitaria, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.

We report here the synthesis of a novel series of 5'-O-carbonates of 3TC, using different aliphatic alcohols and N,N-carbonyldiimidazol. Its antiviral activity was determined in peripheral blood mononuclear cells (PBMCs) showing some carbonate derivatives with an activity similar to or better than 3TC, except 3TC-Metha and 3TC-2Pro with less activity. In vitro assays in PBMCs have demonstrated that cytotoxicity increases as the carbon chain length of the alcohol moiety increases, showing compounds with a normal chain length of n=2-5 good selective index, compared to the parent drug. Thus, this work is an important contribution leading to the suppression of HIV replication.

UI MeSH Term Description Entries
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D001773 Blood Cells The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM. Blood Corpuscles,Blood Cell,Blood Corpuscle,Cell, Blood,Cells, Blood,Corpuscle, Blood,Corpuscles, Blood
D002254 Carbonates Salts or ions of the theoretical carbonic acid, containing the radical CO2(3-). Carbonates are readily decomposed by acids. The carbonates of the alkali metals are water-soluble; all others are insoluble. (From Grant & Hackh's Chemical Dictionary, 5th ed) Carbonate
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
D019259 Lamivudine A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. 2',3'-Dideoxy-3'-thiacytidine,2(1H)-Pyrimidinone, 4-amino-1-(2-(hydroxymethyl)-1,3-oxathiolan-5-yl)-, (2R-cis)-,3TC Lamivudine,Lamivudine, (+)-cis-,Lamivudine, (+-)-trans-,BCH-189,Epivir,GR-109714X,GR109714X,Lamivudine, (2S-cis)-Isomer,2',3' Dideoxy 3' thiacytidine,BCH 189,BCH189,GR 109714X,Lamivudine, 3TC
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

Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
Synthesis and anti-HIV evaluation of new 2',3'-dideoxy-3'-thiacytidine prodrugs.
July 2000, Nucleosides, nucleotides & nucleic acids,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
5'-phosphonate derivatives of 2',3'-dideoxy-3'-thiacytidine as new anti-HIV prodrugs.
July 2011, Chemical biology & drug design,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
Synthesis and biological evaluation of polyaminated 2',3'-dideoxy-3'-thiacytidine prodrugs.
January 1999, Nucleosides & nucleotides,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
New dinucleoside phosphonate derivatives as prodrugs of 3'-azido-3'-deoxythymidine and β-L-2',3'-dideoxy-3'-thiacytidine: synthesis and anti-HIV properties.
January 2014, Nucleosides, nucleotides & nucleic acids,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
Synthesis and antiviral activity of new carbonylphosphonate 2',3'-dideoxy-3'-thiacytidine conjugates.
October 1994, Antiviral research,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
5'-O-ester prodrugs of potent and selective anti-HIV agent--2',3'-dideoxy-3'-fluoro-2-thiothymidine (S2FLT): synthesis and anti-HIV activity.
January 2003, Nucleosides, nucleotides & nucleic acids,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
Phosphatidyl-2',3'-dideoxy-3'-thiacytidine: synthesis and antiviral activity in hepatitis B-and HIV-1-infected cells.
October 1995, Antiviral research,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
Anti-HIV and anti-HBV activity and resistance profile of 2',3'-dideoxy-3'-thiacytidine (3TC) and its arylphosphoramidate derivative CF 1109.
August 1996, Biochemical and biophysical research communications,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides.
December 2012, Bioorganic & medicinal chemistry,
Soledad Ravetti, and María S Gualdesi, and Juan S Trinchero-Hernández, and Gabriela Turk, and Margarita C Briñón
Pharmacokinetics of (-)-2'-3'-dideoxy-3'-thiacytidine in woodchucks.
March 1996, Antimicrobial agents and chemotherapy,
Copied contents to your clipboard!