Discovery of novel N4-alkylcytidines as promising antimicrobial agents

Alexandrova, L. A.; Jasko, Maxim V.; Negrya, Sergey D.; Solyev, Pavel N.; Shevchenko, O. V.; Solodinin, Andrei P.; Kolonitskaya, Daria P.; Karpenko, Inna L.; Efremenkova, Olga V.; Glukhova, A. A.; Boykova, Yuliya V; Ефименко, Т. А.; Кост, Н. В.; Avdanina, Darya; Nuraeva, Gulgina K.; Волков, И. А.; Kochetkov, Sergey N.; Zhgun, A. A.

doi:10.1016/j.ejmech.2021.113212

Cited by 13 publications

(34 citation statements)

References 47 publications

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“…The effect of the alkyl substituent at the N 4 -position of the nucleoside follows the trend of lipophilicity-promoted biocidal activity: increasing the length of the carbohydrate chain results in an increased inhibitory activity: HNC 8 H 17 ≪ HNC 10 H 21 < HNC 12 H 25 . 11 For every variation of the substituent at the 3′-position, the dodecyl radical at the N 4 -position is always correlated with more effective inhibition. In this regard, it can be assumed that dodecyl is the most effective N 4 substituent in the series for creating a fungicidal coating based on the compounds of the studied series.…”

Section: Resultsmentioning

confidence: 97%

“…Compound 2b was used as an internal control since it exhibited the best inhibition profile in our previous work. 11…”

Section: Resultsmentioning

confidence: 99%

“…aAccording to previous data. 11 bN/D – no data.cAbbreviations: amikacin (AN), ciprofloxacin (CIP), isoniazid (INZ), rifampicin (RFP), oxacillin (OX), and vancomycin (VA).…”

Section: Resultsmentioning

confidence: 99%

“…9,10 In this regard, the challenging task is to develop a new generation of biocides that do not damage the materials of the works of art themselves and at the same time retain their effectiveness against many genera of fungi. 11–13…”

Section: Introductionmentioning

confidence: 99%

“…An increase in the length of the alkyl substituent enhances the inhibitory activity to 0.5 mM. 11 As a result, C10 and C12 hydrocarbon chains were selected as the optimal substituents at the N 4 -position of the nucleoside for further investigations.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Section: Resultsmentioning

confidence: 97%

“…Compound 2b was used as an internal control since it exhibited the best inhibition profile in our previous work. 11…”

Section: Resultsmentioning

confidence: 99%

“…aAccording to previous data. 11 bN/D – no data.cAbbreviations: amikacin (AN), ciprofloxacin (CIP), isoniazid (INZ), rifampicin (RFP), oxacillin (OX), and vancomycin (VA).…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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5‐Substituted Uridines with Activity against Gram‐Positive Bacteria

Makarov,

Negrya,

Jasko

et al. 2023

ChemMedChem

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The emergence of drug‐resistant strains of pathogenic microorganisms necessitates the creation of new drugs. A series of uridine derivatives containing an extended substituent at the C‐5 position as well as C‐5 alkyloxymethyl, alkylthiomethyl, alkyltriazolylmethyl, alkylsulfinylmethyl and alkylsulfonylmethyl uridines were obtained in order to explore their antimicrobial properties and solubility. It has been shown that new ribonucleoside derivatives have an order of magnitude better solubility in water compared to their 2'‐deoxy analogues and effectively inhibit the growth of a number of Gram‐positive bacteria, including resistant strains of Mycobacterium smegmatis (MIC = 15–200 μg/ml) and Staphylococcus aureus (MIC = 25–100 μg/ml). Their activity is comparable to that of some antibiotics used in medicine.

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SCRAPPY - a single cell rapid assay of proteome perturbation in yeast uncovers a joint role of aromatic amino acids and oxidative stress in the toxicity of lipophilic nucleoside analogs

Ghazy,

Bidiuk,

Ryabov

et al. 2024

Preprint

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Assaying cellular responses to antimicrobial molecules is a path to understanding modes of action of potential drugs. This is often achieved via transcriptomics and proteomics, but simple and inexpensive methods for rapid characterization are lacking. To bridge this gap, we assayed changes in the abundance of a panel of 64 “sentinel” proteins fused to GFP in the yeastSaccharomyces cerevisiaeusing flow cytometry. This method produced expected patterns for classical antifungals and allowed inference of common mechanisms between known and novel compounds. Single-cell data also revealed diverging responses in mitochondrial protein abundance in response to thiazolidine antifungals, and perturbations of the cell cycle caused by various compounds. Finally, the method provided insight into the unknown mode of action of alkylated nucleosides, which can be used against fungi residing on works of art. These substances elevate levels of proteins involved in the biosynthesis of aromatic amino acids (AAA), as well as in oxidative stress. Furthermore, deficiencies of Trp and Tyr biosynthesis increased the efficacy of these compounds, while antioxidants reduced it. Most surprisingly, antioxidant effectiveness relied on AAA biosynthesis. Thus, our approach and its possible modifications for other microbes provides an easy and reliable platform for revealing modes of action of novel compounds.

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Discovery of novel N4-alkylcytidines as promising antimicrobial agents

Cited by 13 publications

References 47 publications

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

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

5‐Substituted Uridines with Activity against Gram‐Positive Bacteria

SCRAPPY - a single cell rapid assay of proteome perturbation in yeast uncovers a joint role of aromatic amino acids and oxidative stress in the toxicity of lipophilic nucleoside analogs

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Discovery of novel N4-alkylcytidines as promising antimicrobial agents

Cited by 13 publications

References 47 publications

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

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

5‐Substituted Uridines with Activity against Gram‐Positive Bacteria

SCRAPPY - a single cell rapid assay of proteome perturbation in yeast uncovers a joint role of aromatic amino acids and oxidative stress in the toxicity of lipophilic nucleoside analogs

Contact Info

Product

Resources

About

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

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