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在参考和临床细菌菌株上评估的选定 N-取代肉桂酰胺衍生物的抗幽门螺杆菌活性。

Anti-Helicobacter pylori activities of selected N-substituted cinnamamide derivatives evaluated on reference and clinical bacterial strains.

机构信息

Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Kraków, Poland.

Falck Medycyna Outpatient Clinic of Gastroenterology, Mazowiecka 4-6, Kraków, Poland.

出版信息

J Antibiot (Tokyo). 2018 May;71(5):543-548. doi: 10.1038/s41429-018-0027-1. Epub 2018 Feb 13.

Abstract

In this study, thirty-five N-substituted derivatives of cinnamic acid amide (cinnamamide) were evaluated for anti-Helicobacter pylori activity using an agar disc-diffusion method. Qualitative screening was performed on a reference H. pylori strain (ATCC 43504), resulting in the identification of the three most active compounds, 8 (R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide, minimal inhibitory concentration, MIC = 7.5 µg/mL), 23 ((2E)-3-(4-chlorophenyl)-N-(2-hydroxycyclohexyl)prop-2-enamide, MIC = 10 µg/mL), and 28 ((2E)-3-(4-chlorophenyl)-N-(4-oxocyclohexyl)prop-2-enamide, MIC = 10 µg/mL). These compounds were further tested on twelve well-characterized clinical strains, yielding MIC values that ranged from 10 to 1000 µg/mL. Preliminary safety assessments of the compounds were made using the MTT viability test for cytotoxicity and Ames test for mutagenicity, which showed them to be generally safe, although compounds 8 and 28 showed mutagenic activity at some of the tested concentrations. The results of this study showed the anti-H. pylori potential of cinnamamide derivatives.

摘要

在这项研究中,使用琼脂扩散法评估了 35 种 N-取代肉桂酰胺(肉桂酰胺)衍生物的抗幽门螺杆菌活性。对参考幽门螺杆菌菌株(ATCC 43504)进行了定性筛选,鉴定出了三种最活性的化合物,8(R,S-(2E)-3-(4-氯苯基)-N-(2-羟基丙基)丙烯酰胺,最小抑菌浓度,MIC = 7.5 µg/mL),23((2E)-3-(4-氯苯基)-N-(2-羟基环己基)丙烯酰胺,MIC = 10 µg/mL)和 28((2E)-3-(4-氯苯基)-N-(4-氧代环己基)丙烯酰胺,MIC = 10 µg/mL)。这些化合物进一步在 12 种经过充分表征的临床菌株上进行了测试,MIC 值范围为 10 至 1000 µg/mL。使用 MTT 活力试验进行细胞毒性和 Ames 试验进行致突变性的初步安全性评估表明,这些化合物通常是安全的,尽管化合物 8 和 28 在某些测试浓度下表现出致突变活性。这项研究的结果表明了肉桂酰胺衍生物的抗幽门螺杆菌潜力。

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