Fluorinated nucleosides: Synthesis and biological implication

Antiviral and apoptosis modulating potential of fluorinated derivatives of uracil

“…Fluorinated nucleosides exhibit a wide variety of biological activity and have been used extensively as anti-tumor and antiviral agents. Viral polymerase is one of the most common and established targets of nucleoside and the presence of fluoro group makes it unique in terms of their chemical, biological and structural properties [15]. Our research showed that new derivatives of uracil with fluoro group have antiviral activity and might be affected at other enzymes of replication, such as DNA topoisomerase 2, DNA primase/helicase.…”

“…Also, it was established that fluorinated derivatives of uracil (compound G26 and G27) could induce apoptosis in EBV-transformed cell line Raji and B95-8. According to the literary data, nucleoside analogs mimic natural nucleosides in term of uptake and metabolism [15,24]. Further, they can incorporate into newly synthesized DNA resulting in chain termination.…”

“…Further, they can incorporate into newly synthesized DNA resulting in chain termination. Some of these drugs also inhibit key enzymes involved in the biosynthesis of purine and pyrimidine nucleotides and RNA synthesis as well as directly activate the apoptosis as an anti-cancer agent [15]. Also according to the prediction of targets these compounds may interact with different apoptotic proteins such as apoptotic protease-activating factor, MAP kinase, deoxyribonucleotidase (mitochondrial) and some classes of protein kinase.…”

“…These findings suggest the importance of a fluorine moiety in the nucleoside as therapeutic agents. Thymidylate synthase, ribonucleotide diphosphate reductase (RDPR) and viral polymerases are the major targets by fluoronucleosides and fluoroheterocyclic bases [15].…”

GRL-04810 and GRL-05010, Difluoride-Containing Nonpeptidic HIV-1 Protease Inhibitors (PIs) That Inhibit the Replication of Multi-PI-Resistant HIV-1 In Vitro and Possess Favorable Lipophilicity That May Allow Blood-Brain Barrier Penetration

“…The addition of fluorine atoms is generally expected to confer greater lipophilicity on nucleoside analogs and certain compounds (37)(38)(39). Thus, we determined the partition (log P) and distribution (log D) coefficients of GRL-04810 and GRL-05010.…”