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 (12-19) were synthesized and evaluated against Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). The 7-bromo-deazaadenosine analogue (15) demonstrated an EC50 of 0.17 μM and the 7-iodo-deazaadeosine analogue (16) displayed an EC50 of 0.47 μM, compared to ganciclovir (EC50 = 2.5 μM) against EBV. Compound 15 was 14 times more potent than ganciclovir, with a high selectivity index (SI = 294). Additionally, the deazaadenosine analogue (12) and 7-fluoro-deazaadenosine (13) 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 12, 13, 15, and 16 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.