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具有抗革兰氏阳性菌活性的 5-取代尿嘧啶核苷。

5-Substituted Uridines with Activity against Gram-Positive Bacteria.

机构信息

Engelhardt Institute of Molecular Biology RAS, 32 Vavilov str., Moscow, 119991, Russia.

Gause Institute of New Antibiotics, 11 Bol'shaya Pirogovskaya, Moscow, 119021, Russia.

出版信息

ChemMedChem. 2023 Nov 2;18(21):e202300366. doi: 10.1002/cmdc.202300366. Epub 2023 Oct 4.

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.

摘要

为了探索它们的抗菌特性和溶解性,合成了一系列在 C-5 位具有扩展取代基的尿嘧啶衍生物以及 C-5 烷氧基甲基、烷基硫甲基、烷基三唑基甲基、烷基亚砜基甲基和烷基磺酰基甲基尿嘧啶。结果表明,与 2'-脱氧类似物相比,新型核苷衍生物在水中的溶解度提高了一个数量级,并且有效地抑制了多种革兰氏阳性菌的生长,包括抗药性的耻垢分枝杆菌(MIC=15-200μg/mL)和金黄色葡萄球菌(MIC=25-100μg/mL)。它们的活性与一些临床上使用的抗生素相当。

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