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阳离子葡聚糖衍生物对单纯疱疹病毒的抑制作用。

Inhibition of Herpes Simplex Viruses by Cationic Dextran Derivatives.

作者信息

Pachota Magdalena, Klysik Katarzyna, Synowiec Aleksandra, Ciejka Justyna, Szczubiałka Krzysztof, Pyrć Krzysztof, Nowakowska Maria

机构信息

Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , Gronostajowa 7, 30-387 Krakow, Poland.

Malopolska Centre of Biotechnology, Jagiellonian University , Gronostajowa 7A, 30-387 Krakow, Poland.

出版信息

J Med Chem. 2017 Oct 26;60(20):8620-8630. doi: 10.1021/acs.jmedchem.7b01189. Epub 2017 Oct 6.

Abstract

Human herpesviruses are among the most prevalent pathogens and currently there are no drugs available that could cure diseases induced by them. The most widely utilized antiherpes drugs, acyclovir and its derivatives, have serious limitations, such as low bioavailability and severe side effects. The current paper reports on the synthesis and characterization of cationic dextran derivatives (DEXDS) of various molecular weights and various degrees of substitution with ammonium groups, which were tested as antiherpes agents. DEXDS showed high effectiveness against HSV-1 and HSV-2 viruses, as found using a variety of techniques. Importantly, no toxicity was observed for these compounds in the range of active concentrations, demonstrating their potential as antivirals. The mechanism of action of DEXDS was assessed. We hypothesize that they may limit virus transmission, as extensive examination showed that they hamper the interaction between the virus and the cellular attachment receptor.

摘要

人类疱疹病毒是最普遍的病原体之一,目前尚无能够治愈由它们引起的疾病的药物。使用最广泛的抗疱疹药物阿昔洛韦及其衍生物存在严重局限性,如生物利用度低和副作用严重。本文报道了不同分子量和不同铵基取代度的阳离子葡聚糖衍生物(DEXDS)的合成与表征,这些衍生物被作为抗疱疹剂进行了测试。使用多种技术发现,DEXDS对单纯疱疹病毒1型(HSV-1)和单纯疱疹病毒2型(HSV-2)显示出高效性。重要的是,在活性浓度范围内未观察到这些化合物的毒性,证明了它们作为抗病毒药物的潜力。对DEXDS的作用机制进行了评估。我们推测它们可能会限制病毒传播,因为广泛的研究表明它们会阻碍病毒与细胞附着受体之间的相互作用。

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