Synthesis and anti-HIV activity of novel 2',3'-dideoxy-3'-thiacytidine prodrugs.
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.
Ravetti
Soledad
S
Departamento de Farmacia, Facultad de Ciencias Químicas, Ciudad Universitaria, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.
Gualdesi
María S
MS
Trinchero-Hernández
Juan S
JS
Turk
Gabriela
G
Briñón
Margarita C
MC
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001773:Blood Cells / Q000187:drug effects; D002254:Carbonates / Q000737:chemistry; D006801:Humans; D019259:Lamivudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D002254:Carbonates; D011355:Prodrugs; D019259:Lamivudine