SYNTHESIS AND ANTI-HIV ACTIVITY OF NOVEL 2´,3´-DIDEOXY-3´-THIACYTIDINE PRODRUGS

SOLEDAD RAVETTI, MARÍA S. GUALDESI, JUAN S. TRINCHERO-HERNÁNDEZ, GABRIELA TURK, MARGARITA C.

BIOORGANIC & MEDICINAL CHEMISTRY.

ELSEVIER

Lugar: Filadelfia; Año: 2009 vol. 17 p. 6407 - 6413

0968-0896

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 3TCMetha 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.