| Abstract
| - New formamidine-3TC (3TC = 2‘,3‘-dideoxy-3‘-thiacytidine) analogues have been synthesizedthrough various methods, and their antiviral activities (HIV, HBV) have been evaluated invitro. Anti-HIV-1 in acutely infected MT-4 cells and peripheral blood monocellular cells (PBMCs)showed that compounds substituted by N,N-diarylformamidine side chains at the 4-N nucleicbase position (compounds 3 and 8−11) had at least equivalent anti-HIV activity as 3TC (EC50= 0.5 and 11.6 μM, respectively). Moreover, the newly synthesized compounds demonstratedhigher anti-HBV activity (EC50 ranging from 0.01 to 0.05 μM) compared to the parent nucleoside3TC (EC50 = 0.2 μM). It should be underlined that these new promising derivatives inhibitedHIV in cells of a macrophage lineage, which are known to be cellular reservoir for HIV. Theseresults were particularly of interest, since the antiviral activities appeared not to be mediatedthrough the formamidine bond hydrolysis and consequently the release of free 3TC. Thesenew analogue series were found to be highly stable to hydrolysis even after prolonged incubationin different biological media (t1/2 ranged from 48 to 120 h). This enzymatic stability, coupled tothe fact that no delay in the antiviral response was observed compared to the free 3TC antiviralresponse, suggest that this new N,N-diarylformamidine nucleoside series should not beconsidered as classical prodrugs.
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