Abstract
Background: Modified nucleoside and nucleotide analogs are now the cornerstone of antiviral and anticancer chemotherapies. However, these compounds are not active on their own and need, after entering the cell, to be metabolized to their active 5'-triphosphate form.
Methods: Limitations of these metabolic processes led to development of nucleoside/nucleotide prodrugs in which nucleosides are masked with different groups that can be intracellularly cleaved either chemically or enzymatically.
Results: Several prodrug approaches have been successfully developed in order to increase the efficacy, bioavailability, penetration in target organ, and selectivity of nucleoside/nucleotide analogs.
Conclusion: The concept of nucleoside/nucleotide prodrug is now a well-established approach that led to the approval of numerous drugs for the treatment of HIV, HBV, HCV, HSV and cancer.
Keywords: Antiviral agents, prodrug, nucleoside, enzyme, monophosphate, triphosphate.
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