Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides

Shmalenyuk, Eduard R.; Черноусова, Л. Н.; Karpenko, Inna L.; Kochetkov, S. N.; Smirnova, Tatiana G.; Andreevskaya, Sofya; Chizhov, Alexander O.; Efremenkova, Olga V.; Alexandrova, L. А.

doi:10.1016/j.bmc.2013.07.003

Cited by 44 publications

(41 citation statements)

References 35 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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“…In 2013, the same research group synthesized a new set of 5-modified derivatives of pyrimidine 2′-deoxynucleosides containing extended alkyloxymethyl or alkyltriazolidomethyl groups [131]. The most active compounds in this series, 5-dodecyloxy methyl-2′-deoxyuridine (82), 5-decyltriazolidomethyl-2′-deoxyuridine (83), 5-dodecyltriazolidomethyl-2′-deoxyuridine (84) and 5-dodecyltriazolidomethyl-2′-deoxycytidine (85), inhibited with low MIC 99 values (10-50 μg/ml) the growth of wild-type H37Rv and drug-resistant MS-115 ( Figure 14D).…”

Section: Nucleoside Analogs With Unclear Targetmentioning

confidence: 99%

Nucleoside Analogs and Tuberculosis: New Weapons Against an Old Enemy

Ferrari

Serpi

2015

Future Med. Chem.

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Purine and pyrimidine nucleoside and nucleotide analogs have been extensively studied as anticancer and antiviral agents. In addition to this, they have recently shown great potential against Mycobacterium Tuberculosis, the causative agent of TB. TB ranks as the tenth most common cause of death in the world. The current treatment for TB infection is limited by side effects and cost of the drugs and most importantly by the development of resistance to the therapy. Therefore the development of novel drugs, capable of overcoming the drawbacks of the existing treatments, has become the focus of many research programs. In parallel to that, a tremendous effort has been made to elucidate the unique metabolism of this pathogen with the aim to identify new possible targets. This review presents the state of the art in nucleoside and nucleotide analogs in the treatment of TB. In particular, we report on the inhibitory activity of this class of compounds, both in enzymatic and whole-cell assays, providing a brief insight to which reported target these novel compounds are hitting.

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“…Nucleoside derivatives have historically served as potent antiviral and anticancer agents [3], but it was not until 2000 that their anti-TB activity was reported [4]. Recently, several reports of modified nucleosides showing activity against Mycobacterium tuberculosis (M. tuberculosis) , Mycobacterium bovis (M. bovis) and Mycobacterium avium (M. avium) were published [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. Among them, the best activity was observed for several uridine analogues (MIC 90 1 to 10 µg/mL) possessing 5-alkynyl (decynyl, dodecynyl, tetradecynyl, pyridylethynyl, etc.)…”

Section: Introductionmentioning

confidence: 99%

“…In addition, several 2′-deoxypyrimidine derivatives with extended 5-alkyloxymethyl or 5-alkyltriazolylmethyl substituents (5-dodecyloxy-methyl-2′-deoxyuridine, 5-decyltriazolylmethyl-2′-deoxyuridine, 5-dodecyltriazolylmethyl-2′-deoxycytidine, etc.) were shown to inhibit in vitro growth of both laboratory H37Rv and clinical multiple drug resistant (MDR) MS-115 M. tuberculosis strains with MIC 99 values ~10 µg/mL (Figure 1) [5].…”

Section: Introductionmentioning

confidence: 99%

Novel 5′-Norcarbocyclic Pyrimidine Derivatives as Antibacterial Agents

et al. 2018

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A series of novel 5′-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of Mycobacterium smegmatis was completely inhibited by the most active compounds at a MIC99 of 67 μg/mL (mc2155) and a MIC99 of 6.7–67 μg/mL (VKPM Ac 1339). Several compounds also showed the ability to inhibit the growth of attenuated strains of Mycobacterium tuberculosis ATCC 25177 (MIC99 28–61 μg/mL) and Mycobacterium bovis ATCC 35737 (MIC99 50–60 μg/mL), as well as two virulent strains of M. tuberculosis; a laboratory strain H37Rv (MIC99 20–50 μg/mL) and a clinical strain with multiple drug resistance MS-115 (MIC99 20–50 μg/mL). Transmission electron microscopy (TEM) evaluation of M. tuberculosis H37Rv bacterial cells treated with one of the compounds demonstrated destruction of the bacterial cell wall, suggesting that the mechanism of action for these compounds may be related to their interactions with bacteria cell walls.

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Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides

Cited by 44 publications

References 35 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

Nucleoside Analogs and Tuberculosis: New Weapons Against an Old Enemy

Novel 5′-Norcarbocyclic Pyrimidine Derivatives as Antibacterial Agents

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