Oligoglycol carbonate prodrugs of 5-modified 2'-deoxyuridines: synthesis and antibacterial activity

Negrya, Sergey D.; Jasko, Maxim V.; Makarov, D. A.; Karpenko, Inna L.; Solyev, Pavel N.; Chekhov, V. O.; Efremenkova, Olga V.; Vasilieva, Byasilya F.; Ефименко, Т. А.; Kochetkov, Sergey N.; Alexandrova, L. A.

doi:10.1016/j.mencom.2022.07.002

Cited by 5 publications

(6 citation statements)

References 21 publications

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“…Previously, to solve the problem of bioavailability, we obtained prodrug forms of these compounds (Figure 5), which demonstrated a significant inhibitory effect against Grampositive bacteria (including mycobacteria) as well. [35][36][37] In the case of new ribonucleoside derivatives having bulky substituents at the C-5 position of the nucleobase, the presence of an additional hydroxy group at the 2'-position of the carbohydrate moiety, as expected, increased their solubility (Table 4).…”

Section: Water Solubilitymentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

“…Previously obtained prodrug forms of 2'-deoxyuridine. [35][36][37] organic media and for studying their biological properties, therefore it wasn't necessary to obtain their prodrug forms. The highest solubility in water was shown by the compound (�)-5 c containing the sulfinylmethyl group (Table 4).…”

Section: Water Solubilitymentioning

confidence: 99%

“…Calculated spatial patterns of (+)-5(m) and (À )-5(m) for two molecules of (+)-5 d and (À )-5 d diastereomers.Figure5. Previously obtained prodrug forms of 2'-deoxyuridine [35][36][37].…”

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confidence: 99%

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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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Section: Water Solubilitymentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Water Solubilitymentioning

confidence: 99%

“…Calculated spatial patterns of (+)-5(m) and (À )-5(m) for two molecules of (+)-5 d and (À )-5 d diastereomers.Figure5. Previously obtained prodrug forms of 2'-deoxyuridine [35][36][37].…”

mentioning

confidence: 99%

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5‐Substituted Uridines with Activity against Gram‐Positive Bacteria

Makarov,

Negrya,

Jasko

et al. 2023

ChemMedChem

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“…In order to develop a new set of antibacterial nucleosides, a representative library [72][73][74] of 3′-and 5′-trior tetraethylene glycol prodrugs of 5-alkyloxymethyl-and 5alkyltriazolylmethyl-2′-deoxyuridines with described antituberculosis activity were synthesized (Figure 10) [42,43]. The compounds were two orders of magnitude more soluble compared to the parent nucleosides, had significant inhibitory activity against a number of bacteria, including drug-resistant strains of M. smegmatis (as well as S. aureus), and exhibited low cytotoxicity [72][73][74]. The replacement of the triethylene glycol residue in C-5′ position by tetraethylene glycol led to an increase in water solubility and a significant decrease in inhibitory activity.…”

Section: Depot Forms Depot Forms With Increased Solubilitymentioning

confidence: 99%

Pyrimidine Nucleosides Analogues as Mycobacteria Growth Inhibitors

Alexandrova¹,

Khandazhinskaya²,

Matyugina³

et al. 2022

Which Factors Contribute to Innovative Performance? A Case Study Applied to the Food and Beverage Industry

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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 multidrugresistant 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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