5-(4-alkyl-1,2,3-triazol-1-yl)methyl derivatives of 2′-deoxyuridine as inhibitors of viral and bacterial growth

Alexandrova, L. A.; Efremenkova, Olga V.; Андронова, В. Л.; Галегов, Г. А.; Solyev, Pavel N.; Karpenko, Inna L.; Kochetkov, S. N.

doi:10.1134/s1068162016050022

Cited by 19 publications

(12 citation statements)

References 16 publications

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“…Nucleoside analogues containing substituted 1,2,3-triazole moieties at the C5′ position of the ribofuranose residue demonstrated significant anticancer activity against cancer cell lines A549, HT-29, MCF-7, A-375 and/or antibacterial and antifungal activities [26,27]. Pyrimidine nucleoside analogues in which a 1,2,3-triazole ring was attached either directly to the C5 position of 2′-deoxyuridine or via a methylene unit were synthesized and exhibited both antiviral activity against herpes simplex viruses, varicella-zoster virus, human cytomegalovirus, vaccinia virus [28][29][30][31] and significant anticancer effects against cancer cell lines PC-3, MDA-MB-231, ACHN [28]. Recently, a series of nucleoside analogues in which the pyrimidine fragment was attached to the ribose moiety at the C1′ carbon via a 1,2,3-triazolyl bridge has been synthesized [32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

et al. 2020

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Based on the fact that a search for influenza antivirals among nucleoside analogues has drawn very little attention of chemists, the present study reports the synthesis of a series of 1,2,3-triazolyl nucleoside analogues in which a pyrimidine fragment is attached to the ribofuranosyl-1,2,3-triazol-4-yl moiety by a polymethylene linker of variable length. Target compounds were prepared by the Cu alkyne-azide cycloaddition (CuAAC) reaction. Derivatives of uracil, 6-methyluracil, 3,6-dimethyluracil, thymine and quinazolin-2,4-dione with ω-alkyne substituent at the N1 (or N5) atom and azido 2,3,5-triO -acetyl-D-β-ribofuranoside were used as components of the CuAAC reaction. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. The best values of IC 50 (inhibiting concentration) and SI (selectivity index) were demonstrated by the lead compound 4i in which the 1,2,3-triazolylribofuranosyl fragment is attached to the N1 atom of the quinazoline-2,4-dione moiety via a butylene linker (IC 50 = 30 μM, SI = 24) and compound 8n in which the 1,2,3-triazolylribofuranosyl fragment is attached directly to the N5 atom of the 6-methyluracil moiety (IC 50 = 15 μM, SI = 5). According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 4i and 8n against H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRP).

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Section: Introductionmentioning

confidence: 99%

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

et al. 2020

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“…The antibacterial effect of our synthesized compounds was studied in vitro by their ability to inhibit the microorganism growth. [34][35][36] The antibacterial assay was carried out against such Gram-positive bacteria, such as Bacillus subtilis, two strains of Staphylococcus aureus, streptococcus-like bacteria Leuconostoc mesenteroides and Micrococcus luteus, and two strains of Mycobacterium smegmatis, and Gram-negative bacteria including Escherichia coli and Pseudomonas aeruginosa. 3 0 -Modified N 4 -alkyl-5-methyl-2 0 ,3 0 -dideoxycytidines demonstrate activity against Gram-positive bacteria as well as mycobacteria (Table 1), and there is no activity against Gram-negative microorganisms (with the exception of N 4 -dodecyl-3 0 -amino-5-methyl-2 0 ,3 0 -dideoxycytidine 10b, which also showed high inhibitory activity against Gram-negative bacteria, E. coli (49 mM)).…”

Section: Biological Evaluation and Structure-activity Relationship St...mentioning

confidence: 99%

3′-Amino modifications enhance the antifungal properties of N⁴-alkyl-5-methylcytidines for potential biocides

et al. 2022

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“…Described compounds containing long hydrophobic groups are poorly soluble in water-organic solutions. At the same time, better soluble 5-alkyltriazolylmethyl-2′-deoxyuridines with short alkyl residues, in contrast to decyl- and dodecyl-triazolylmethyl-2′-deoxyuridines, demonstrated antibacterial activity against a number of Gram-positive bacteria [ 46 ]. On the other hand, 2′-deoxyuridine derivatives containing long hydrophilic substituents 26a , b in the 5-position (which is similar to a chain of 10–12 atoms in the C-5 position of the pyrimidine base of the nucleosides that previously showed the best anti-tuberculosis activity) were well-soluble compounds, but completely lost antimicrobial activity [ 47 ].…”

Section: Inhibitors Of M Tuberculosis Growth With ...mentioning

confidence: 99%

Analogues of Pyrimidine Nucleosides as Mycobacteria Growth Inhibitors

et al. 2022

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Tuberculosis (TB) is the oldest human infection disease. Mortality from TB significantly decreased in the 20th century, because of vaccination and the widespread use of antibiotics. However, about a third of the world’s population is currently infected with Mycobacterium tuberculosis (Mtb) and the death rate from TB is about 1.4–2 million people per year. In the second half of the 20th century, new extensively multidrug-resistant strains of Mtb were identified, which are steadily increasing among TB patients. Therefore, there is an urgent need to develop new anti-TB drugs, which remains one of the priorities of pharmacology and medicinal chemistry. The antimycobacterial activity of nucleoside derivatives and analogues was revealed not so long ago, and a lot of studies on their antibacterial properties have been published. Despite the fact that there are no clinically used drugs based on nucleoside analogues, some progress has been made in this area. This review summarizes current research in the field of the design and study of inhibitors of mycobacteria, primarily Mtb.

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5-(4-alkyl-1,2,3-triazol-1-yl)methyl derivatives of 2′-deoxyuridine as inhibitors of viral and bacterial growth

Cited by 19 publications

References 16 publications

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

3′-Amino modifications enhance the antifungal properties of N⁴-alkyl-5-methylcytidines for potential biocides

Analogues of Pyrimidine Nucleosides as Mycobacteria Growth Inhibitors

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5-(4-alkyl-1,2,3-triazol-1-yl)methyl derivatives of 2′-deoxyuridine as inhibitors of viral and bacterial growth

Cited by 19 publications

References 16 publications

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

3′-Amino modifications enhance the antifungal properties of N4-alkyl-5-methylcytidines for potential biocides

Analogues of Pyrimidine Nucleosides as Mycobacteria Growth Inhibitors

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3′-Amino modifications enhance the antifungal properties of N⁴-alkyl-5-methylcytidines for potential biocides