Synthesis and Antiviral Evaluation of Unexplored Dioxolane-Derived 7-Deazapurine Nucleoside Analogues against Epstein–Barr Virus (EBV)

Dioxolane-based nucleosides are characterized by their unique replacement of the sugar moiety by dioxolane-based cyclopentyl rings. A series of d-dioxolane-derived 7-deazapurine analogues (<b>12</b>-<b>19</b>) were synthesized and evaluated against Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). The 7-bromo-deazaadenosine analogue (<b>15</b>) demonstrated an EC₅₀ of 0.17 μM and the 7-iodo-deazaadeosine analogue (<b>16</b>) displayed an EC₅₀ of 0.47 μM, compared to ganciclovir (EC₅₀ = 2.5 μM) against EBV. Compound <b>15</b> was 14 times more potent than ganciclovir, with a high selectivity index (SI = 294). Additionally, the deazaadenosine analogue (<b>12</b>) and 7-fluoro-deazaadenosine (<b>13</b>) have shown moderate antiviral potency against HIV. The reported analogues of this series expressed both potency and selectivity against EBV. The development of prodrugs for analogues <b>12</b>, <b>13</b>, <b>15</b>, and <b>16</b> may potentially enhance their antiviral activity against EBV and HIV, offering a promising avenue for identifying preclinical candidates effective against both DNA and RNA viruses.