5-Substituted Uridines with Activity against Gram-Positive Bacteria

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL ChemMedChem Pub Date : 2023-09-14 DOI:10.1002/cmdc.202300366

Dmitry A. Makarov, Dr. Sergey D. Negrya, Maxim V. Jasko, Dr. Inna L. Karpenko, Dr. Pavel N. Solyev, Dr. Vladimir O. Chekhov, Dr. Dmitry N. Kaluzhny, Dr. Olga V. Efremenkova, Byazilya F. Vasilyeva, Dr. Alexander O. Chizhov, Dr. Darya A. Avdanina, Dr. Alexander A. Zhgun, Prof. Sergey N. Kochetkov, Dr. Liudmila A. Alexandrova

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Abstract

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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具有抗革兰氏阳性菌活性的5-取代尿苷

病原微生物耐药菌株的出现要求研制新药。为了研究其抗菌性能和溶解度，制备了一系列含有C-5扩展取代基的尿嘧啶衍生物，以及C-5烷基氧基甲基、烷基硫甲基、烷基三唑基甲基、烷基亚砜基甲基和烷基磺酰甲基尿嘧啶。研究表明，新的核糖核苷衍生物在水中的溶解度比它们的2 ' -脱氧类似物好一个数量级，并能有效抑制革兰氏阳性细菌的生长，包括耐药菌株耻垢分枝杆菌(MIC= 15-200 μg/mL)和金黄色葡萄球菌(MIC= 25-100 μg/mL)。它们的活性与医学上使用的一些抗生素相当。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.