Anti-Tick-Borne Encephalitis Virus Activity of Novel Uridine Glycoconjugates Containing Amide or/and 1,2,3-Triazole Moiety in the Linker Structure

Abstract

Tick-borne encephalitis virus (TBEV) transmitted by ticks is a pathogen of great medical importance. As still no effective antiviral treatment is available, in the present study, a series of uridine glycoconjugates containing amide or/and 1,2,3-triazole moiety in the linker structure was synthesized and evaluated for the antiviral activity against two strains of TBEV: a highly virulent Hypr strain and less virulent Neudoerfl strain, using standardized previously in vitro assays. Our data have shown that four compounds from the series (18–21) possess strong activity against both TBEV strains. The half maximal inhibitory concentration (IC50) values of compounds 18–21 were between 15.1 and 3.7 μM depending on the virus strain, which along with low cytotoxicity resulted in high values of the selectivity index (SI). The obtained results suggest that these compounds may be promising candidates for further development of new therapies against flaviviruses.

Synthesis and Antiproliferative Evaluation of d‐Glucuronamide‐Based Nucleosides and (Triazolyl)methyl Amide‐Linked Pseudodisaccharide Nucleosides**

“…[11] Scheme 2. system in which CuI is supported on Amberlyst A21 resin. [33] In both cases, dimethylaminopurine pseudodisaccharide nucleosides (20,22) were obtained in modest similar yields (27 %-29 %) along with their 5-iodotriazole derivatives as secondary products (21, 23, 23 % and 9 % yields, respectively, Scheme 3).…”

“…[11] More recently, the synthesis and antiflaviviral potential of 1,5-linked pseudodisaccharide nucleoside analogues of such type of structures were reported. [22] 6-Chloropurine N-propargyl glucuronamide-containing nucleoside analogues of compound A possessing a 3-O-dodecyl group, which may increase the cell-penetrating ability of the molecules, were accessed, aiming at evaluating the effect of moving the dodecyl moiety from the amide system to a hydroxyl group on the antiproliferative activity of the molecules. Moreover, analogues of A comprising a novel type of dglucopyranuronamide-based nucleosidic framework having a methylene 1,2,3-triazolyl fragment between the 6-chloropurine system and the glucuronamide moiety, i. e. (purinyl)methyltriazole nucleosides were accessed.…”

“…Per‐ O ‐acetylated N ‐propargyl glucuronamide‐based nucleosides were also converted into corresponding (triazolyl)methyl amide‐6,6‐linked pseudodisaccharide nucleosides to further assess the anticancer potential of this type of structure, which was firstly proposed by us as potential mimetic of nucleoside diphosphate sugars in which the (triazolyl)methyl amide system is proposed as a surrogate of the diphosphate moiety [11] . More recently, the synthesis and antiflaviviral potential of 1,5‐linked pseudodisaccharide nucleoside analogues of such type of structures were reported [22] …”

Synthesis and Antiproliferative Evaluation of Novel D-Glucuronamide-based Nucleosides and (Triazolyl)methyl Amide-linked Pseudodisaccharide Nucleosides

“…Per-O-acetylated N-propargyl glucuronamide-based nucleosides were also converted into corresponding (triazolyl)methyl amide-6,6-linked pseudodisaccharide nucleosides to further assess the anticancer potential of this type of structure, which was firstly proposed by us as potential mimetic of nucleoside diphosphate sugars in which the (triazolyl)methyl amide system is proposed a surrogate of the diphosphate moiety [11]. More recently, the synthesis and antiflaviviral potential of 1,5-linked pseudodisaccharide nucleoside analogues of such type of structures were reported [22]. 6-Chloropurine N-propargyl glucuronamide-containing nucleoside analogues of compound A possessing a 3-O-dodecyl group, which may increase the cell-penetrating ability of the molecules, were accessed, aiming at evaluating the effect of moving the dodecyl moiety from the amide system to a hydroxyl group on the antiproliferative activity of the molecules.…”

Searching Anti-Zika Virus Activity in 1H-1,2,3-Triazole Based Compounds

“…These three classes of compounds, namely 1,4-naphthoquinone, phthalimide and 1,2,3-triazole inspired our research. These moieties have biological activities against several infections [18][19][20], including ZIKV [21,22]. Our group has synthesized several heterocycle derivatives and tested their activities against human cancer cell lines [23][24][25].…”